ModernModern treatmenttreatment of of pancreaticpancreatic cancercancer 2009 2009 updateupdate

Morten LadekarlDepartment of Oncology

Aarhus University HospitalDenmark

Resectable diseaseLocally advanced diseaseAdvanced disease

Supportive carePancreatic neuro-endocrine tumours

RESECTABLE DISEASE

Disease stage 5-year survival ()

Localized 152

Regional 68

Distant 18

SEER Cancer Statistics Review 1975-2001

RESECTABLE DISEASE

CONKOCONKO--001001 Gem Gem vsvs observationobservation

RESECTABLE DISEASE

Significant increase in median survival from Significant increase in median survival from 20 to 2320 to 23 monthsmonthsIncrease in est 5Increase in est 5--year survival rate from year survival rate from 9 to 219 to 21Beneficial effect in all subgroupsBeneficial effect in all subgroups

Oettle et al JAMA 2007 amp Neuhaus et al ASCO proceedings 2008

ESPACESPAC‐‐33ESPAC‐3 A multicenter international open‐label randomized controlled

phase

III trial

of adjuvant

5‐fluorouracilfolinic

acid

(5‐FUFA) versus gemcitabine

(GEM) in patients with

resected

pancreatic

ductal

adenocarcinoma

Neoptolemos

et al

ASCO 2009

Gemcitabin

1 gang om ugen i

6 cyklusN=537

5FU+ folinsyre

i 5 dage hver

28 dag i 6 cyklusN=551

1088 pt

RESECTABLE DISEASE

3 arm BSC lukket pr3 arm BSC lukket praeligaeligmaturt grundet signifikant effekt af Gem maturt grundet signifikant effekt af Gem vsvs BSCBSCR0R1 R0R1 resektionresektion lt 8 uger efter operationlt 8 uger efter operation

ESPACESPAC‐‐33ESPAC‐3 A multicenter international open‐label randomized controlled

phase

III trial

of adjuvant

5‐fluorouracilfolinic

acid

(5‐FUFA) versus gemcitabine

(GEM) in patients with

resected

pancreatic

ductal

adenocarcinoma

Neoptolemos

et al

RESECTABLE DISEASE

News 2009 News 2009 adjuvantadjuvant treatmenttreatment

bullbull Gem Gem ogog 5FU 5FU erer ligelige effektiveeffektive men Gem men Gem erer mindstmindst toksisktoksisk

bullbull GemCapGemCap

vs Gem er i fase III (ESPACvs Gem er i fase III (ESPAC‐‐4)4)

RESECTABLE DISEASE

LOCALLY ADVANCED DISEASELOCALLY ADVANCED DISEASE

OptionsOptions

bullbull ChemotherapyChemotherapyndashndash GemGemndashndash Gem in combinationsGem in combinations

bullbull ChemoradiotherapyChemoradiotherapy

LOCALLY ADVANCED DISEASE

Overall survival on GemOverall survival on Gem

Storinolo et al Cancer 1998

LOCALLY ADVANCED DISEASE

ChauffertChauffert et alet al Phase IIIPhase III--study of Gem vs 5FUcisplatinstudy of Gem vs 5FUcisplatin--based CRTbased CRT

LOCALLY ADVANCED DISEASE

LOCALLY ADVANCED DISEASE

ChauffertChauffert et alet al Phase IIIPhase III--study of Gem vs 5FUcisplatinstudy of Gem vs 5FUcisplatin--based CRTbased CRT

LOCALLY ADVANCED DISEASE

LoehrerLoehrer et alet al Phase IIIPhase III--study of Gem vs Gemstudy of Gem vs Gem--based CRTbased CRT

LOCALLY ADVANCED DISEASE

LoehrerLoehrer et alet al Phase IIIPhase III--study of Gem vs Gemstudy of Gem vs Gem--based CRTbased CRT

LOCALLY ADVANCED DISEASE

Wilkowski

et al Final analysis

of a multicenter randomized

phase

II trial

comparing

three

different

chemoradiotherapy

regimens

in the treatment

of patients with

locally

advanced nonmetastatic

pancreatic

cancer ASCO 2009

Cis‐gemDag 1 8 22 29

Og cis‐gem

efter KRT

Kontinuerlig 5FU

Cis‐gemDag 18 22 2995 pt

ndashndash 3 forskellige kemo3 forskellige kemo‐‐regimer med regimer med konkomittantkonkomittant

strstraringaringlebehandling lebehandling aacuteaacute 50GY25fr 50GY25fr

LOCALLY ADVANCED DISEASE

Final analysis

of a multicenter randomized

phase

II trial

comparing

three

different

chemoradiotherapy

regimens

in the

treatment

of patients with

locally

advanced nonmetastatic

pancreatic

cancer Ralf

Wilkowski

bull 18 patienter blev opereret Fordeling ukendtbull Hoslashjere frekvens af grad 34 haeligmotologiske

bivirkninger i GC armene

bull Ingen forskel mellem 5FU og GemCis

PFSPFS((mdrmdr))

OSOS((mdrmdr))

HHaeligaeligmtoxmtox DiarreDiarre

RKTRKT--5FU5FU 44 9696 ++RKTRKT--GCGC 5656 9393 ++RKTRKT--GC + GCGC + GC 66 7373 ++

LOCALLY ADVANCED DISEASE

RESECTABLE DISEASE

Disease stage 5-year survival ()

Localized 152

Regional 68

Distant 18

SEER Cancer Statistics Review 1975-2001

RESECTABLE DISEASE

CONKOCONKO--001001 Gem Gem vsvs observationobservation

RESECTABLE DISEASE

Significant increase in median survival from Significant increase in median survival from 20 to 2320 to 23 monthsmonthsIncrease in est 5Increase in est 5--year survival rate from year survival rate from 9 to 219 to 21Beneficial effect in all subgroupsBeneficial effect in all subgroups

Oettle et al JAMA 2007 amp Neuhaus et al ASCO proceedings 2008

ESPACESPAC‐‐33ESPAC‐3 A multicenter international open‐label randomized controlled

phase

III trial

of adjuvant

5‐fluorouracilfolinic

acid

(5‐FUFA) versus gemcitabine

(GEM) in patients with

resected

pancreatic

ductal

adenocarcinoma

Neoptolemos

et al

ASCO 2009

Gemcitabin

1 gang om ugen i

6 cyklusN=537

5FU+ folinsyre

i 5 dage hver

28 dag i 6 cyklusN=551

1088 pt

RESECTABLE DISEASE

3 arm BSC lukket pr3 arm BSC lukket praeligaeligmaturt grundet signifikant effekt af Gem maturt grundet signifikant effekt af Gem vsvs BSCBSCR0R1 R0R1 resektionresektion lt 8 uger efter operationlt 8 uger efter operation

ESPACESPAC‐‐33ESPAC‐3 A multicenter international open‐label randomized controlled

phase

III trial

of adjuvant

5‐fluorouracilfolinic

acid

(5‐FUFA) versus gemcitabine

(GEM) in patients with

resected

pancreatic

ductal

adenocarcinoma

Neoptolemos

et al

RESECTABLE DISEASE

News 2009 News 2009 adjuvantadjuvant treatmenttreatment

bullbull Gem Gem ogog 5FU 5FU erer ligelige effektiveeffektive men Gem men Gem erer mindstmindst toksisktoksisk

bullbull GemCapGemCap

vs Gem er i fase III (ESPACvs Gem er i fase III (ESPAC‐‐4)4)

RESECTABLE DISEASE

LOCALLY ADVANCED DISEASELOCALLY ADVANCED DISEASE

OptionsOptions

bullbull ChemotherapyChemotherapyndashndash GemGemndashndash Gem in combinationsGem in combinations

bullbull ChemoradiotherapyChemoradiotherapy

LOCALLY ADVANCED DISEASE

Overall survival on GemOverall survival on Gem

Storinolo et al Cancer 1998

LOCALLY ADVANCED DISEASE

ChauffertChauffert et alet al Phase IIIPhase III--study of Gem vs 5FUcisplatinstudy of Gem vs 5FUcisplatin--based CRTbased CRT

LOCALLY ADVANCED DISEASE

LOCALLY ADVANCED DISEASE

ChauffertChauffert et alet al Phase IIIPhase III--study of Gem vs 5FUcisplatinstudy of Gem vs 5FUcisplatin--based CRTbased CRT

LOCALLY ADVANCED DISEASE

LoehrerLoehrer et alet al Phase IIIPhase III--study of Gem vs Gemstudy of Gem vs Gem--based CRTbased CRT

LOCALLY ADVANCED DISEASE

LoehrerLoehrer et alet al Phase IIIPhase III--study of Gem vs Gemstudy of Gem vs Gem--based CRTbased CRT

LOCALLY ADVANCED DISEASE

Wilkowski

et al Final analysis

of a multicenter randomized

phase

II trial

comparing

three

different

chemoradiotherapy

regimens

in the treatment

of patients with

locally

advanced nonmetastatic

pancreatic

cancer ASCO 2009

Cis‐gemDag 1 8 22 29

Og cis‐gem

efter KRT

Kontinuerlig 5FU

Cis‐gemDag 18 22 2995 pt

ndashndash 3 forskellige kemo3 forskellige kemo‐‐regimer med regimer med konkomittantkonkomittant

strstraringaringlebehandling lebehandling aacuteaacute 50GY25fr 50GY25fr

LOCALLY ADVANCED DISEASE

Final analysis

of a multicenter randomized

phase

II trial

comparing

three

different

chemoradiotherapy

regimens

in the

treatment

of patients with

locally

advanced nonmetastatic

pancreatic

cancer Ralf

Wilkowski

bull 18 patienter blev opereret Fordeling ukendtbull Hoslashjere frekvens af grad 34 haeligmotologiske

bivirkninger i GC armene

bull Ingen forskel mellem 5FU og GemCis

PFSPFS((mdrmdr))

OSOS((mdrmdr))

HHaeligaeligmtoxmtox DiarreDiarre

RKTRKT--5FU5FU 44 9696 ++RKTRKT--GCGC 5656 9393 ++RKTRKT--GC + GCGC + GC 66 7373 ++

LOCALLY ADVANCED DISEASE

Disease stage 5-year survival ()

Localized 152

Regional 68

Distant 18

SEER Cancer Statistics Review 1975-2001

RESECTABLE DISEASE

CONKOCONKO--001001 Gem Gem vsvs observationobservation

RESECTABLE DISEASE

Significant increase in median survival from Significant increase in median survival from 20 to 2320 to 23 monthsmonthsIncrease in est 5Increase in est 5--year survival rate from year survival rate from 9 to 219 to 21Beneficial effect in all subgroupsBeneficial effect in all subgroups

Oettle et al JAMA 2007 amp Neuhaus et al ASCO proceedings 2008

ESPACESPAC‐‐33ESPAC‐3 A multicenter international open‐label randomized controlled

phase

III trial

of adjuvant

5‐fluorouracilfolinic

acid

(5‐FUFA) versus gemcitabine

(GEM) in patients with

resected

pancreatic

ductal

adenocarcinoma

Neoptolemos

et al

ASCO 2009

Gemcitabin

1 gang om ugen i

6 cyklusN=537

5FU+ folinsyre

i 5 dage hver

28 dag i 6 cyklusN=551

1088 pt

RESECTABLE DISEASE

3 arm BSC lukket pr3 arm BSC lukket praeligaeligmaturt grundet signifikant effekt af Gem maturt grundet signifikant effekt af Gem vsvs BSCBSCR0R1 R0R1 resektionresektion lt 8 uger efter operationlt 8 uger efter operation

ESPACESPAC‐‐33ESPAC‐3 A multicenter international open‐label randomized controlled

phase

III trial

of adjuvant

5‐fluorouracilfolinic

acid

(5‐FUFA) versus gemcitabine

(GEM) in patients with

resected

pancreatic

ductal

adenocarcinoma

Neoptolemos

et al

RESECTABLE DISEASE

News 2009 News 2009 adjuvantadjuvant treatmenttreatment

bullbull Gem Gem ogog 5FU 5FU erer ligelige effektiveeffektive men Gem men Gem erer mindstmindst toksisktoksisk

bullbull GemCapGemCap

vs Gem er i fase III (ESPACvs Gem er i fase III (ESPAC‐‐4)4)

RESECTABLE DISEASE

LOCALLY ADVANCED DISEASELOCALLY ADVANCED DISEASE

OptionsOptions

bullbull ChemotherapyChemotherapyndashndash GemGemndashndash Gem in combinationsGem in combinations

bullbull ChemoradiotherapyChemoradiotherapy

LOCALLY ADVANCED DISEASE

Overall survival on GemOverall survival on Gem

Storinolo et al Cancer 1998

LOCALLY ADVANCED DISEASE

ChauffertChauffert et alet al Phase IIIPhase III--study of Gem vs 5FUcisplatinstudy of Gem vs 5FUcisplatin--based CRTbased CRT

LOCALLY ADVANCED DISEASE

LOCALLY ADVANCED DISEASE

ChauffertChauffert et alet al Phase IIIPhase III--study of Gem vs 5FUcisplatinstudy of Gem vs 5FUcisplatin--based CRTbased CRT

LOCALLY ADVANCED DISEASE

LoehrerLoehrer et alet al Phase IIIPhase III--study of Gem vs Gemstudy of Gem vs Gem--based CRTbased CRT

LOCALLY ADVANCED DISEASE

LoehrerLoehrer et alet al Phase IIIPhase III--study of Gem vs Gemstudy of Gem vs Gem--based CRTbased CRT

LOCALLY ADVANCED DISEASE

Wilkowski

et al Final analysis

of a multicenter randomized

phase

II trial

comparing

three

different

chemoradiotherapy

regimens

in the treatment

of patients with

locally

advanced nonmetastatic

pancreatic

cancer ASCO 2009

Cis‐gemDag 1 8 22 29

Og cis‐gem

efter KRT

Kontinuerlig 5FU

Cis‐gemDag 18 22 2995 pt

ndashndash 3 forskellige kemo3 forskellige kemo‐‐regimer med regimer med konkomittantkonkomittant

strstraringaringlebehandling lebehandling aacuteaacute 50GY25fr 50GY25fr

LOCALLY ADVANCED DISEASE

Final analysis

of a multicenter randomized

phase

II trial

comparing

three

different

chemoradiotherapy

regimens

in the

treatment

of patients with

locally

advanced nonmetastatic

pancreatic

cancer Ralf

Wilkowski

bull 18 patienter blev opereret Fordeling ukendtbull Hoslashjere frekvens af grad 34 haeligmotologiske

bivirkninger i GC armene

bull Ingen forskel mellem 5FU og GemCis

PFSPFS((mdrmdr))

OSOS((mdrmdr))

HHaeligaeligmtoxmtox DiarreDiarre

RKTRKT--5FU5FU 44 9696 ++RKTRKT--GCGC 5656 9393 ++RKTRKT--GC + GCGC + GC 66 7373 ++

LOCALLY ADVANCED DISEASE

CONKOCONKO--001001 Gem Gem vsvs observationobservation

RESECTABLE DISEASE

Significant increase in median survival from Significant increase in median survival from 20 to 2320 to 23 monthsmonthsIncrease in est 5Increase in est 5--year survival rate from year survival rate from 9 to 219 to 21Beneficial effect in all subgroupsBeneficial effect in all subgroups

Oettle et al JAMA 2007 amp Neuhaus et al ASCO proceedings 2008

ESPACESPAC‐‐33ESPAC‐3 A multicenter international open‐label randomized controlled

phase

III trial

of adjuvant

5‐fluorouracilfolinic

acid

(5‐FUFA) versus gemcitabine

(GEM) in patients with

resected

pancreatic

ductal

adenocarcinoma

Neoptolemos

et al

ASCO 2009

Gemcitabin

1 gang om ugen i

6 cyklusN=537

5FU+ folinsyre

i 5 dage hver

28 dag i 6 cyklusN=551

1088 pt

RESECTABLE DISEASE

3 arm BSC lukket pr3 arm BSC lukket praeligaeligmaturt grundet signifikant effekt af Gem maturt grundet signifikant effekt af Gem vsvs BSCBSCR0R1 R0R1 resektionresektion lt 8 uger efter operationlt 8 uger efter operation

ESPACESPAC‐‐33ESPAC‐3 A multicenter international open‐label randomized controlled

phase

III trial

of adjuvant

5‐fluorouracilfolinic

acid

(5‐FUFA) versus gemcitabine

(GEM) in patients with

resected

pancreatic

ductal

adenocarcinoma

Neoptolemos

et al

RESECTABLE DISEASE

News 2009 News 2009 adjuvantadjuvant treatmenttreatment

bullbull Gem Gem ogog 5FU 5FU erer ligelige effektiveeffektive men Gem men Gem erer mindstmindst toksisktoksisk

bullbull GemCapGemCap

vs Gem er i fase III (ESPACvs Gem er i fase III (ESPAC‐‐4)4)

RESECTABLE DISEASE

LOCALLY ADVANCED DISEASELOCALLY ADVANCED DISEASE

OptionsOptions

bullbull ChemotherapyChemotherapyndashndash GemGemndashndash Gem in combinationsGem in combinations

bullbull ChemoradiotherapyChemoradiotherapy

LOCALLY ADVANCED DISEASE

Overall survival on GemOverall survival on Gem

Storinolo et al Cancer 1998

LOCALLY ADVANCED DISEASE

ChauffertChauffert et alet al Phase IIIPhase III--study of Gem vs 5FUcisplatinstudy of Gem vs 5FUcisplatin--based CRTbased CRT

LOCALLY ADVANCED DISEASE

LOCALLY ADVANCED DISEASE

ChauffertChauffert et alet al Phase IIIPhase III--study of Gem vs 5FUcisplatinstudy of Gem vs 5FUcisplatin--based CRTbased CRT

LOCALLY ADVANCED DISEASE

LoehrerLoehrer et alet al Phase IIIPhase III--study of Gem vs Gemstudy of Gem vs Gem--based CRTbased CRT

LOCALLY ADVANCED DISEASE

LoehrerLoehrer et alet al Phase IIIPhase III--study of Gem vs Gemstudy of Gem vs Gem--based CRTbased CRT

LOCALLY ADVANCED DISEASE

Wilkowski

et al Final analysis

of a multicenter randomized

phase

II trial

comparing

three

different

chemoradiotherapy

regimens

in the treatment

of patients with

locally

advanced nonmetastatic

pancreatic

cancer ASCO 2009

Cis‐gemDag 1 8 22 29

Og cis‐gem

efter KRT

Kontinuerlig 5FU

Cis‐gemDag 18 22 2995 pt

ndashndash 3 forskellige kemo3 forskellige kemo‐‐regimer med regimer med konkomittantkonkomittant

strstraringaringlebehandling lebehandling aacuteaacute 50GY25fr 50GY25fr

LOCALLY ADVANCED DISEASE

Final analysis

of a multicenter randomized

phase

II trial

comparing

three

different

chemoradiotherapy

regimens

in the

treatment

of patients with

locally

advanced nonmetastatic

pancreatic

cancer Ralf

Wilkowski

bull 18 patienter blev opereret Fordeling ukendtbull Hoslashjere frekvens af grad 34 haeligmotologiske

bivirkninger i GC armene

bull Ingen forskel mellem 5FU og GemCis

PFSPFS((mdrmdr))

OSOS((mdrmdr))

HHaeligaeligmtoxmtox DiarreDiarre

RKTRKT--5FU5FU 44 9696 ++RKTRKT--GCGC 5656 9393 ++RKTRKT--GC + GCGC + GC 66 7373 ++

LOCALLY ADVANCED DISEASE

ESPACESPAC‐‐33ESPAC‐3 A multicenter international open‐label randomized controlled

phase

III trial

of adjuvant

5‐fluorouracilfolinic

acid

(5‐FUFA) versus gemcitabine

(GEM) in patients with

resected

pancreatic

ductal

adenocarcinoma

Neoptolemos

et al

ASCO 2009

Gemcitabin

1 gang om ugen i

6 cyklusN=537

5FU+ folinsyre

i 5 dage hver

28 dag i 6 cyklusN=551

1088 pt

RESECTABLE DISEASE

3 arm BSC lukket pr3 arm BSC lukket praeligaeligmaturt grundet signifikant effekt af Gem maturt grundet signifikant effekt af Gem vsvs BSCBSCR0R1 R0R1 resektionresektion lt 8 uger efter operationlt 8 uger efter operation

ESPACESPAC‐‐33ESPAC‐3 A multicenter international open‐label randomized controlled

phase

III trial

of adjuvant

5‐fluorouracilfolinic

acid

(5‐FUFA) versus gemcitabine

(GEM) in patients with

resected

pancreatic

ductal

adenocarcinoma

Neoptolemos

et al

RESECTABLE DISEASE

News 2009 News 2009 adjuvantadjuvant treatmenttreatment

bullbull Gem Gem ogog 5FU 5FU erer ligelige effektiveeffektive men Gem men Gem erer mindstmindst toksisktoksisk

bullbull GemCapGemCap

vs Gem er i fase III (ESPACvs Gem er i fase III (ESPAC‐‐4)4)

RESECTABLE DISEASE

LOCALLY ADVANCED DISEASELOCALLY ADVANCED DISEASE

OptionsOptions

bullbull ChemotherapyChemotherapyndashndash GemGemndashndash Gem in combinationsGem in combinations

bullbull ChemoradiotherapyChemoradiotherapy

LOCALLY ADVANCED DISEASE

Overall survival on GemOverall survival on Gem

Storinolo et al Cancer 1998

LOCALLY ADVANCED DISEASE

ChauffertChauffert et alet al Phase IIIPhase III--study of Gem vs 5FUcisplatinstudy of Gem vs 5FUcisplatin--based CRTbased CRT

LOCALLY ADVANCED DISEASE

LOCALLY ADVANCED DISEASE

ChauffertChauffert et alet al Phase IIIPhase III--study of Gem vs 5FUcisplatinstudy of Gem vs 5FUcisplatin--based CRTbased CRT

LOCALLY ADVANCED DISEASE

LoehrerLoehrer et alet al Phase IIIPhase III--study of Gem vs Gemstudy of Gem vs Gem--based CRTbased CRT

LOCALLY ADVANCED DISEASE

LoehrerLoehrer et alet al Phase IIIPhase III--study of Gem vs Gemstudy of Gem vs Gem--based CRTbased CRT

LOCALLY ADVANCED DISEASE

Wilkowski

et al Final analysis

of a multicenter randomized

phase

II trial

comparing

three

different

chemoradiotherapy

regimens

in the treatment

of patients with

locally

advanced nonmetastatic

pancreatic

cancer ASCO 2009

Cis‐gemDag 1 8 22 29

Og cis‐gem

efter KRT

Kontinuerlig 5FU

Cis‐gemDag 18 22 2995 pt

ndashndash 3 forskellige kemo3 forskellige kemo‐‐regimer med regimer med konkomittantkonkomittant

strstraringaringlebehandling lebehandling aacuteaacute 50GY25fr 50GY25fr

LOCALLY ADVANCED DISEASE

Final analysis

of a multicenter randomized

phase

II trial

comparing

three

different

chemoradiotherapy

regimens

in the

treatment

of patients with

locally

advanced nonmetastatic

pancreatic

cancer Ralf

Wilkowski

bull 18 patienter blev opereret Fordeling ukendtbull Hoslashjere frekvens af grad 34 haeligmotologiske

bivirkninger i GC armene

bull Ingen forskel mellem 5FU og GemCis

PFSPFS((mdrmdr))

OSOS((mdrmdr))

HHaeligaeligmtoxmtox DiarreDiarre

RKTRKT--5FU5FU 44 9696 ++RKTRKT--GCGC 5656 9393 ++RKTRKT--GC + GCGC + GC 66 7373 ++

LOCALLY ADVANCED DISEASE

ESPACESPAC‐‐33ESPAC‐3 A multicenter international open‐label randomized controlled

phase

III trial

of adjuvant

5‐fluorouracilfolinic

acid

(5‐FUFA) versus gemcitabine

(GEM) in patients with

resected

pancreatic

ductal

adenocarcinoma

Neoptolemos

et al

RESECTABLE DISEASE

News 2009 News 2009 adjuvantadjuvant treatmenttreatment

bullbull Gem Gem ogog 5FU 5FU erer ligelige effektiveeffektive men Gem men Gem erer mindstmindst toksisktoksisk

bullbull GemCapGemCap

vs Gem er i fase III (ESPACvs Gem er i fase III (ESPAC‐‐4)4)

RESECTABLE DISEASE

LOCALLY ADVANCED DISEASELOCALLY ADVANCED DISEASE

OptionsOptions

bullbull ChemotherapyChemotherapyndashndash GemGemndashndash Gem in combinationsGem in combinations

bullbull ChemoradiotherapyChemoradiotherapy

LOCALLY ADVANCED DISEASE

Overall survival on GemOverall survival on Gem

Storinolo et al Cancer 1998

LOCALLY ADVANCED DISEASE

ChauffertChauffert et alet al Phase IIIPhase III--study of Gem vs 5FUcisplatinstudy of Gem vs 5FUcisplatin--based CRTbased CRT

LOCALLY ADVANCED DISEASE

LOCALLY ADVANCED DISEASE

ChauffertChauffert et alet al Phase IIIPhase III--study of Gem vs 5FUcisplatinstudy of Gem vs 5FUcisplatin--based CRTbased CRT

LOCALLY ADVANCED DISEASE

LoehrerLoehrer et alet al Phase IIIPhase III--study of Gem vs Gemstudy of Gem vs Gem--based CRTbased CRT

LOCALLY ADVANCED DISEASE

LoehrerLoehrer et alet al Phase IIIPhase III--study of Gem vs Gemstudy of Gem vs Gem--based CRTbased CRT

LOCALLY ADVANCED DISEASE

Wilkowski

et al Final analysis

of a multicenter randomized

phase

II trial

comparing

three

different

chemoradiotherapy

regimens

in the treatment

of patients with

locally

advanced nonmetastatic

pancreatic

cancer ASCO 2009

Cis‐gemDag 1 8 22 29

Og cis‐gem

efter KRT

Kontinuerlig 5FU

Cis‐gemDag 18 22 2995 pt

ndashndash 3 forskellige kemo3 forskellige kemo‐‐regimer med regimer med konkomittantkonkomittant

strstraringaringlebehandling lebehandling aacuteaacute 50GY25fr 50GY25fr

LOCALLY ADVANCED DISEASE

Final analysis

of a multicenter randomized

phase

II trial

comparing

three

different

chemoradiotherapy

regimens

in the

treatment

of patients with

locally

advanced nonmetastatic

pancreatic

cancer Ralf

Wilkowski

bull 18 patienter blev opereret Fordeling ukendtbull Hoslashjere frekvens af grad 34 haeligmotologiske

bivirkninger i GC armene

bull Ingen forskel mellem 5FU og GemCis

PFSPFS((mdrmdr))

OSOS((mdrmdr))

HHaeligaeligmtoxmtox DiarreDiarre

RKTRKT--5FU5FU 44 9696 ++RKTRKT--GCGC 5656 9393 ++RKTRKT--GC + GCGC + GC 66 7373 ++

LOCALLY ADVANCED DISEASE

News 2009 News 2009 adjuvantadjuvant treatmenttreatment

bullbull Gem Gem ogog 5FU 5FU erer ligelige effektiveeffektive men Gem men Gem erer mindstmindst toksisktoksisk

bullbull GemCapGemCap

vs Gem er i fase III (ESPACvs Gem er i fase III (ESPAC‐‐4)4)

RESECTABLE DISEASE

LOCALLY ADVANCED DISEASELOCALLY ADVANCED DISEASE

OptionsOptions

bullbull ChemotherapyChemotherapyndashndash GemGemndashndash Gem in combinationsGem in combinations

bullbull ChemoradiotherapyChemoradiotherapy

LOCALLY ADVANCED DISEASE

Overall survival on GemOverall survival on Gem

Storinolo et al Cancer 1998

LOCALLY ADVANCED DISEASE

ChauffertChauffert et alet al Phase IIIPhase III--study of Gem vs 5FUcisplatinstudy of Gem vs 5FUcisplatin--based CRTbased CRT

LOCALLY ADVANCED DISEASE

LOCALLY ADVANCED DISEASE

ChauffertChauffert et alet al Phase IIIPhase III--study of Gem vs 5FUcisplatinstudy of Gem vs 5FUcisplatin--based CRTbased CRT

LOCALLY ADVANCED DISEASE

LoehrerLoehrer et alet al Phase IIIPhase III--study of Gem vs Gemstudy of Gem vs Gem--based CRTbased CRT

LOCALLY ADVANCED DISEASE

LoehrerLoehrer et alet al Phase IIIPhase III--study of Gem vs Gemstudy of Gem vs Gem--based CRTbased CRT

LOCALLY ADVANCED DISEASE

Wilkowski

et al Final analysis

of a multicenter randomized

phase

II trial

comparing

three

different

chemoradiotherapy

regimens

in the treatment

of patients with

locally

advanced nonmetastatic

pancreatic

cancer ASCO 2009

Cis‐gemDag 1 8 22 29

Og cis‐gem

efter KRT

Kontinuerlig 5FU

Cis‐gemDag 18 22 2995 pt

ndashndash 3 forskellige kemo3 forskellige kemo‐‐regimer med regimer med konkomittantkonkomittant

strstraringaringlebehandling lebehandling aacuteaacute 50GY25fr 50GY25fr

LOCALLY ADVANCED DISEASE

Final analysis

of a multicenter randomized

phase

II trial

comparing

three

different

chemoradiotherapy

regimens

in the

treatment

of patients with

locally

advanced nonmetastatic

pancreatic

cancer Ralf

Wilkowski

bull 18 patienter blev opereret Fordeling ukendtbull Hoslashjere frekvens af grad 34 haeligmotologiske

bivirkninger i GC armene

bull Ingen forskel mellem 5FU og GemCis

PFSPFS((mdrmdr))

OSOS((mdrmdr))

HHaeligaeligmtoxmtox DiarreDiarre

RKTRKT--5FU5FU 44 9696 ++RKTRKT--GCGC 5656 9393 ++RKTRKT--GC + GCGC + GC 66 7373 ++

LOCALLY ADVANCED DISEASE

LOCALLY ADVANCED DISEASELOCALLY ADVANCED DISEASE

OptionsOptions

bullbull ChemotherapyChemotherapyndashndash GemGemndashndash Gem in combinationsGem in combinations

bullbull ChemoradiotherapyChemoradiotherapy

LOCALLY ADVANCED DISEASE

Overall survival on GemOverall survival on Gem

Storinolo et al Cancer 1998

LOCALLY ADVANCED DISEASE

ChauffertChauffert et alet al Phase IIIPhase III--study of Gem vs 5FUcisplatinstudy of Gem vs 5FUcisplatin--based CRTbased CRT

LOCALLY ADVANCED DISEASE

LOCALLY ADVANCED DISEASE

ChauffertChauffert et alet al Phase IIIPhase III--study of Gem vs 5FUcisplatinstudy of Gem vs 5FUcisplatin--based CRTbased CRT

LOCALLY ADVANCED DISEASE

LoehrerLoehrer et alet al Phase IIIPhase III--study of Gem vs Gemstudy of Gem vs Gem--based CRTbased CRT

LOCALLY ADVANCED DISEASE

LoehrerLoehrer et alet al Phase IIIPhase III--study of Gem vs Gemstudy of Gem vs Gem--based CRTbased CRT

LOCALLY ADVANCED DISEASE

Wilkowski

et al Final analysis

of a multicenter randomized

phase

II trial

comparing

three

different

chemoradiotherapy

regimens

in the treatment

of patients with

locally

advanced nonmetastatic

pancreatic

cancer ASCO 2009

Cis‐gemDag 1 8 22 29

Og cis‐gem

efter KRT

Kontinuerlig 5FU

Cis‐gemDag 18 22 2995 pt

ndashndash 3 forskellige kemo3 forskellige kemo‐‐regimer med regimer med konkomittantkonkomittant

strstraringaringlebehandling lebehandling aacuteaacute 50GY25fr 50GY25fr

LOCALLY ADVANCED DISEASE

Final analysis

of a multicenter randomized

phase

II trial

comparing

three

different

chemoradiotherapy

regimens

in the

treatment

of patients with

locally

advanced nonmetastatic

pancreatic

cancer Ralf

Wilkowski

bull 18 patienter blev opereret Fordeling ukendtbull Hoslashjere frekvens af grad 34 haeligmotologiske

bivirkninger i GC armene

bull Ingen forskel mellem 5FU og GemCis

PFSPFS((mdrmdr))

OSOS((mdrmdr))

HHaeligaeligmtoxmtox DiarreDiarre

RKTRKT--5FU5FU 44 9696 ++RKTRKT--GCGC 5656 9393 ++RKTRKT--GC + GCGC + GC 66 7373 ++

LOCALLY ADVANCED DISEASE

OptionsOptions

bullbull ChemotherapyChemotherapyndashndash GemGemndashndash Gem in combinationsGem in combinations

bullbull ChemoradiotherapyChemoradiotherapy

LOCALLY ADVANCED DISEASE

Overall survival on GemOverall survival on Gem

Storinolo et al Cancer 1998

LOCALLY ADVANCED DISEASE

ChauffertChauffert et alet al Phase IIIPhase III--study of Gem vs 5FUcisplatinstudy of Gem vs 5FUcisplatin--based CRTbased CRT

LOCALLY ADVANCED DISEASE

LOCALLY ADVANCED DISEASE

ChauffertChauffert et alet al Phase IIIPhase III--study of Gem vs 5FUcisplatinstudy of Gem vs 5FUcisplatin--based CRTbased CRT

LOCALLY ADVANCED DISEASE

LoehrerLoehrer et alet al Phase IIIPhase III--study of Gem vs Gemstudy of Gem vs Gem--based CRTbased CRT

LOCALLY ADVANCED DISEASE

LoehrerLoehrer et alet al Phase IIIPhase III--study of Gem vs Gemstudy of Gem vs Gem--based CRTbased CRT

LOCALLY ADVANCED DISEASE

Wilkowski

et al Final analysis

of a multicenter randomized

phase

II trial

comparing

three

different

chemoradiotherapy

regimens

in the treatment

of patients with

locally

advanced nonmetastatic

pancreatic

cancer ASCO 2009

Cis‐gemDag 1 8 22 29

Og cis‐gem

efter KRT

Kontinuerlig 5FU

Cis‐gemDag 18 22 2995 pt

ndashndash 3 forskellige kemo3 forskellige kemo‐‐regimer med regimer med konkomittantkonkomittant

strstraringaringlebehandling lebehandling aacuteaacute 50GY25fr 50GY25fr

LOCALLY ADVANCED DISEASE

Final analysis

of a multicenter randomized

phase

II trial

comparing

three

different

chemoradiotherapy

regimens

in the

treatment

of patients with

locally

advanced nonmetastatic

pancreatic

cancer Ralf

Wilkowski

bull 18 patienter blev opereret Fordeling ukendtbull Hoslashjere frekvens af grad 34 haeligmotologiske

bivirkninger i GC armene

bull Ingen forskel mellem 5FU og GemCis

PFSPFS((mdrmdr))

OSOS((mdrmdr))

HHaeligaeligmtoxmtox DiarreDiarre

RKTRKT--5FU5FU 44 9696 ++RKTRKT--GCGC 5656 9393 ++RKTRKT--GC + GCGC + GC 66 7373 ++

LOCALLY ADVANCED DISEASE

Overall survival on GemOverall survival on Gem

Storinolo et al Cancer 1998

LOCALLY ADVANCED DISEASE

ChauffertChauffert et alet al Phase IIIPhase III--study of Gem vs 5FUcisplatinstudy of Gem vs 5FUcisplatin--based CRTbased CRT

LOCALLY ADVANCED DISEASE

LOCALLY ADVANCED DISEASE

ChauffertChauffert et alet al Phase IIIPhase III--study of Gem vs 5FUcisplatinstudy of Gem vs 5FUcisplatin--based CRTbased CRT

LOCALLY ADVANCED DISEASE

LoehrerLoehrer et alet al Phase IIIPhase III--study of Gem vs Gemstudy of Gem vs Gem--based CRTbased CRT

LOCALLY ADVANCED DISEASE

LoehrerLoehrer et alet al Phase IIIPhase III--study of Gem vs Gemstudy of Gem vs Gem--based CRTbased CRT

LOCALLY ADVANCED DISEASE

Wilkowski

et al Final analysis

of a multicenter randomized

phase

II trial

comparing

three

different

chemoradiotherapy

regimens

in the treatment

of patients with

locally

advanced nonmetastatic

pancreatic

cancer ASCO 2009

Cis‐gemDag 1 8 22 29

Og cis‐gem

efter KRT

Kontinuerlig 5FU

Cis‐gemDag 18 22 2995 pt

ndashndash 3 forskellige kemo3 forskellige kemo‐‐regimer med regimer med konkomittantkonkomittant

strstraringaringlebehandling lebehandling aacuteaacute 50GY25fr 50GY25fr

LOCALLY ADVANCED DISEASE

Final analysis

of a multicenter randomized

phase

II trial

comparing

three

different

chemoradiotherapy

regimens

in the

treatment

of patients with

locally

advanced nonmetastatic

pancreatic

cancer Ralf

Wilkowski

bull 18 patienter blev opereret Fordeling ukendtbull Hoslashjere frekvens af grad 34 haeligmotologiske

bivirkninger i GC armene

bull Ingen forskel mellem 5FU og GemCis

PFSPFS((mdrmdr))

OSOS((mdrmdr))

HHaeligaeligmtoxmtox DiarreDiarre

RKTRKT--5FU5FU 44 9696 ++RKTRKT--GCGC 5656 9393 ++RKTRKT--GC + GCGC + GC 66 7373 ++

LOCALLY ADVANCED DISEASE

ChauffertChauffert et alet al Phase IIIPhase III--study of Gem vs 5FUcisplatinstudy of Gem vs 5FUcisplatin--based CRTbased CRT

LOCALLY ADVANCED DISEASE

LOCALLY ADVANCED DISEASE

ChauffertChauffert et alet al Phase IIIPhase III--study of Gem vs 5FUcisplatinstudy of Gem vs 5FUcisplatin--based CRTbased CRT

LOCALLY ADVANCED DISEASE

LoehrerLoehrer et alet al Phase IIIPhase III--study of Gem vs Gemstudy of Gem vs Gem--based CRTbased CRT

LOCALLY ADVANCED DISEASE

LoehrerLoehrer et alet al Phase IIIPhase III--study of Gem vs Gemstudy of Gem vs Gem--based CRTbased CRT

LOCALLY ADVANCED DISEASE

Wilkowski

et al Final analysis

of a multicenter randomized

phase

II trial

comparing

three

different

chemoradiotherapy

regimens

in the treatment

of patients with

locally

advanced nonmetastatic

pancreatic

cancer ASCO 2009

Cis‐gemDag 1 8 22 29

Og cis‐gem

efter KRT

Kontinuerlig 5FU

Cis‐gemDag 18 22 2995 pt

ndashndash 3 forskellige kemo3 forskellige kemo‐‐regimer med regimer med konkomittantkonkomittant

strstraringaringlebehandling lebehandling aacuteaacute 50GY25fr 50GY25fr

LOCALLY ADVANCED DISEASE

Final analysis

of a multicenter randomized

phase

II trial

comparing

three

different

chemoradiotherapy

regimens

in the

treatment

of patients with

locally

advanced nonmetastatic

pancreatic

cancer Ralf

Wilkowski

bull 18 patienter blev opereret Fordeling ukendtbull Hoslashjere frekvens af grad 34 haeligmotologiske

bivirkninger i GC armene

bull Ingen forskel mellem 5FU og GemCis

PFSPFS((mdrmdr))

OSOS((mdrmdr))

HHaeligaeligmtoxmtox DiarreDiarre

RKTRKT--5FU5FU 44 9696 ++RKTRKT--GCGC 5656 9393 ++RKTRKT--GC + GCGC + GC 66 7373 ++

LOCALLY ADVANCED DISEASE

LOCALLY ADVANCED DISEASE

ChauffertChauffert et alet al Phase IIIPhase III--study of Gem vs 5FUcisplatinstudy of Gem vs 5FUcisplatin--based CRTbased CRT

LOCALLY ADVANCED DISEASE

LoehrerLoehrer et alet al Phase IIIPhase III--study of Gem vs Gemstudy of Gem vs Gem--based CRTbased CRT

LOCALLY ADVANCED DISEASE

LoehrerLoehrer et alet al Phase IIIPhase III--study of Gem vs Gemstudy of Gem vs Gem--based CRTbased CRT

LOCALLY ADVANCED DISEASE

Wilkowski

et al Final analysis

of a multicenter randomized

phase

II trial

comparing

three

different

chemoradiotherapy

regimens

in the treatment

of patients with

locally

advanced nonmetastatic

pancreatic

cancer ASCO 2009

Cis‐gemDag 1 8 22 29

Og cis‐gem

efter KRT

Kontinuerlig 5FU

Cis‐gemDag 18 22 2995 pt

ndashndash 3 forskellige kemo3 forskellige kemo‐‐regimer med regimer med konkomittantkonkomittant

strstraringaringlebehandling lebehandling aacuteaacute 50GY25fr 50GY25fr

LOCALLY ADVANCED DISEASE

Final analysis

of a multicenter randomized

phase

II trial

comparing

three

different

chemoradiotherapy

regimens

in the

treatment

of patients with

locally

advanced nonmetastatic

pancreatic

cancer Ralf

Wilkowski

bull 18 patienter blev opereret Fordeling ukendtbull Hoslashjere frekvens af grad 34 haeligmotologiske

bivirkninger i GC armene

bull Ingen forskel mellem 5FU og GemCis

PFSPFS((mdrmdr))

OSOS((mdrmdr))

HHaeligaeligmtoxmtox DiarreDiarre

RKTRKT--5FU5FU 44 9696 ++RKTRKT--GCGC 5656 9393 ++RKTRKT--GC + GCGC + GC 66 7373 ++

LOCALLY ADVANCED DISEASE

ChauffertChauffert et alet al Phase IIIPhase III--study of Gem vs 5FUcisplatinstudy of Gem vs 5FUcisplatin--based CRTbased CRT

LOCALLY ADVANCED DISEASE

LoehrerLoehrer et alet al Phase IIIPhase III--study of Gem vs Gemstudy of Gem vs Gem--based CRTbased CRT

LOCALLY ADVANCED DISEASE

LoehrerLoehrer et alet al Phase IIIPhase III--study of Gem vs Gemstudy of Gem vs Gem--based CRTbased CRT

LOCALLY ADVANCED DISEASE

Wilkowski

et al Final analysis

of a multicenter randomized

phase

II trial

comparing

three

different

chemoradiotherapy

regimens

in the treatment

of patients with

locally

advanced nonmetastatic

pancreatic

cancer ASCO 2009

Cis‐gemDag 1 8 22 29

Og cis‐gem

efter KRT

Kontinuerlig 5FU

Cis‐gemDag 18 22 2995 pt

ndashndash 3 forskellige kemo3 forskellige kemo‐‐regimer med regimer med konkomittantkonkomittant

strstraringaringlebehandling lebehandling aacuteaacute 50GY25fr 50GY25fr

LOCALLY ADVANCED DISEASE

Final analysis

of a multicenter randomized

phase

II trial

comparing

three

different

chemoradiotherapy

regimens

in the

treatment

of patients with

locally

advanced nonmetastatic

pancreatic

cancer Ralf

Wilkowski

bull 18 patienter blev opereret Fordeling ukendtbull Hoslashjere frekvens af grad 34 haeligmotologiske

bivirkninger i GC armene

bull Ingen forskel mellem 5FU og GemCis

PFSPFS((mdrmdr))

OSOS((mdrmdr))

HHaeligaeligmtoxmtox DiarreDiarre

RKTRKT--5FU5FU 44 9696 ++RKTRKT--GCGC 5656 9393 ++RKTRKT--GC + GCGC + GC 66 7373 ++

LOCALLY ADVANCED DISEASE

LoehrerLoehrer et alet al Phase IIIPhase III--study of Gem vs Gemstudy of Gem vs Gem--based CRTbased CRT

LOCALLY ADVANCED DISEASE

LoehrerLoehrer et alet al Phase IIIPhase III--study of Gem vs Gemstudy of Gem vs Gem--based CRTbased CRT

LOCALLY ADVANCED DISEASE

Wilkowski

et al Final analysis

of a multicenter randomized

phase

II trial

comparing

three

different

chemoradiotherapy

regimens

in the treatment

of patients with

locally

advanced nonmetastatic

pancreatic

cancer ASCO 2009

Cis‐gemDag 1 8 22 29

Og cis‐gem

efter KRT

Kontinuerlig 5FU

Cis‐gemDag 18 22 2995 pt

ndashndash 3 forskellige kemo3 forskellige kemo‐‐regimer med regimer med konkomittantkonkomittant

strstraringaringlebehandling lebehandling aacuteaacute 50GY25fr 50GY25fr

LOCALLY ADVANCED DISEASE

Final analysis

of a multicenter randomized

phase

II trial

comparing

three

different

chemoradiotherapy

regimens

in the

treatment

of patients with

locally

advanced nonmetastatic

pancreatic

cancer Ralf

Wilkowski

bull 18 patienter blev opereret Fordeling ukendtbull Hoslashjere frekvens af grad 34 haeligmotologiske

bivirkninger i GC armene

bull Ingen forskel mellem 5FU og GemCis

PFSPFS((mdrmdr))

OSOS((mdrmdr))

HHaeligaeligmtoxmtox DiarreDiarre

RKTRKT--5FU5FU 44 9696 ++RKTRKT--GCGC 5656 9393 ++RKTRKT--GC + GCGC + GC 66 7373 ++

LOCALLY ADVANCED DISEASE

LoehrerLoehrer et alet al Phase IIIPhase III--study of Gem vs Gemstudy of Gem vs Gem--based CRTbased CRT

LOCALLY ADVANCED DISEASE

Wilkowski

et al Final analysis

of a multicenter randomized

phase

II trial

comparing

three

different

chemoradiotherapy

regimens

in the treatment

of patients with

locally

advanced nonmetastatic

pancreatic

cancer ASCO 2009

Cis‐gemDag 1 8 22 29

Og cis‐gem

efter KRT

Kontinuerlig 5FU

Cis‐gemDag 18 22 2995 pt

ndashndash 3 forskellige kemo3 forskellige kemo‐‐regimer med regimer med konkomittantkonkomittant

strstraringaringlebehandling lebehandling aacuteaacute 50GY25fr 50GY25fr

LOCALLY ADVANCED DISEASE

Final analysis

of a multicenter randomized

phase

II trial

comparing

three

different

chemoradiotherapy

regimens

in the

treatment

of patients with

locally

advanced nonmetastatic

pancreatic

cancer Ralf

Wilkowski

bull 18 patienter blev opereret Fordeling ukendtbull Hoslashjere frekvens af grad 34 haeligmotologiske

bivirkninger i GC armene

bull Ingen forskel mellem 5FU og GemCis

PFSPFS((mdrmdr))

OSOS((mdrmdr))

HHaeligaeligmtoxmtox DiarreDiarre

RKTRKT--5FU5FU 44 9696 ++RKTRKT--GCGC 5656 9393 ++RKTRKT--GC + GCGC + GC 66 7373 ++

LOCALLY ADVANCED DISEASE

Wilkowski

et al Final analysis

of a multicenter randomized

phase

II trial

comparing

three

different

chemoradiotherapy

regimens

in the treatment

of patients with

locally

advanced nonmetastatic

pancreatic

cancer ASCO 2009

Cis‐gemDag 1 8 22 29

Og cis‐gem

efter KRT

Kontinuerlig 5FU

Cis‐gemDag 18 22 2995 pt

ndashndash 3 forskellige kemo3 forskellige kemo‐‐regimer med regimer med konkomittantkonkomittant

strstraringaringlebehandling lebehandling aacuteaacute 50GY25fr 50GY25fr

LOCALLY ADVANCED DISEASE

Final analysis

of a multicenter randomized

phase

II trial

comparing

three

different

chemoradiotherapy

regimens

in the

treatment

of patients with

locally

advanced nonmetastatic

pancreatic

cancer Ralf

Wilkowski

bull 18 patienter blev opereret Fordeling ukendtbull Hoslashjere frekvens af grad 34 haeligmotologiske

bivirkninger i GC armene

bull Ingen forskel mellem 5FU og GemCis

PFSPFS((mdrmdr))

OSOS((mdrmdr))

HHaeligaeligmtoxmtox DiarreDiarre

RKTRKT--5FU5FU 44 9696 ++RKTRKT--GCGC 5656 9393 ++RKTRKT--GC + GCGC + GC 66 7373 ++

LOCALLY ADVANCED DISEASE

Final analysis

of a multicenter randomized

phase

II trial

comparing

three

different

chemoradiotherapy

regimens

in the

treatment

of patients with

locally

advanced nonmetastatic

pancreatic

cancer Ralf

Wilkowski

bull 18 patienter blev opereret Fordeling ukendtbull Hoslashjere frekvens af grad 34 haeligmotologiske

bivirkninger i GC armene

bull Ingen forskel mellem 5FU og GemCis

PFSPFS((mdrmdr))

OSOS((mdrmdr))

HHaeligaeligmtoxmtox DiarreDiarre

RKTRKT--5FU5FU 44 9696 ++RKTRKT--GCGC 5656 9393 ++RKTRKT--GC + GCGC + GC 66 7373 ++

LOCALLY ADVANCED DISEASE

KonklusionerKonklusioner

bullbull StadigStadig ikkeikke afklaretafklaret omom kemokemo--radioterapiradioterapi forlforlaeligaeligngernger overlevelsenoverlevelsen i i forholdforhold tiltil kemoterapikemoterapi alenealene

bullbull IkkeIkke afklaretafklaret hvilkenhvilken kemoterapikemoterapi derder erer bedstbedst sammensammen med med radioterapiradioterapi

bullbull KemoKemo--radioterapiradioterapi kankan i i udvalgteudvalgte tilftilfaeligaeligldelde medfmedfoslashoslashrere konverteringkonvertering afaf sygdomsygdom frafra ikkeikke--resektabelresektabel tiltil resektabelresektabel men men detdet kankan kemoterapikemoterapi alenealene ogsogsaringaring

LOCALLY ADVANCED DISEASE

Herrmann 2008

LOCALLY ADVANCED DISEASE

ADVANCED DISEASEADVANCED DISEASE

AdvancedAdvanced diseasedisease

bullbull Median Median survivalsurvival untreateduntreated 33--4 4 monthsmonthsbullbull PrimaryPrimary goalsgoals of of treatmenttreatment

ndashndash Prolongation of Prolongation of survivalsurvivalndashndash ImprovementImprovement in in QoLQoL

ADVANCED DISEASE

GemcitabineGemcitabine vs 5vs 5--FUFU

Burris H et al J Clin Oncol 1997152403-2413

Gemcitabine 5-FU P

Clinical benefit response 24 5 0002 Median survival (months) 57 44 0002 Time to progression (months) 21 09 0001 6-month survival 46 31 1-year survival 18 2 Partial response 54 0 Stable disease 393 19 Composite of measurements of pain (analgesic consumption and pain intensity) Karnofsky

performance status and weight

ADVANCED DISEASE

SurvivalSurvival of of GemGem--treatedtreated patients patients accordingaccording to performance statusto performance status

Storinolo et al Cancer 1998

ADVANCED DISEASE

Combination chemotherapyCombination chemotherapy GemGem--CapCap

JCO october 2009

ADVANCED DISEASE

CunninghamCunningham et al GEMet al GEM--CAPCAP

Hazard ratio 080 95 CI 065ndash098Log-rank p=0026

Eur J Cancer Suppl 2005

Interim analysis 2005Final analysis 2009

ADVANCED DISEASE

MetaMeta--analysisanalysis of GEMof GEM--CAPCAP

Cunningham et al JCO 2009

ADVANCED DISEASE

Gem vs Gem vs GemGem‐‐platinumplatinumDi Miao A randomized

trial

of gemcitabine

(G) versus G plus cisplatin

in chemotherapy‐naive

advanced

pancreatic

adenocarcinoma The GIP‐1 (Gruppo

Italiano Pancreasmdash

GOIMGISCADGOIRC)

study

ASCO 2009

Gemcitabin

som kontrol +

cisplatin

ugentlig 25mgm2N=201

Gemcitabin

ugentlig i 7 uger

2 ugers pause og dag 18 15 i

4 ugers cyklusN=199

400 pt

ADVANCED DISEASE

GemGem GemCisGemCis

OSOS11‐‐year year survivalsurvivalPFSPFS

AnAnaeligaeligmimiTrombocytopeniTrombocytopeni

83 mdr 83 mdr 340 340 39 mdr 39 mdr

39392929

72 mdr 72 mdr 307 307 38 mdr38 mdr

50505757

A randomized

trial

of gemcitabine

(G) versus G plus cisplatin

in chemotherapy‐naive

advanced

pancreatic

adenocarcinoma

The GIP‐1 (Gruppo

Italiano Pancreasmdash

GOIMGISCADGOIRC)

study

Di Miao

bull Alle endepunkter insignifikantebull Subgruppeanalyse

af PS 0 Signifikant negativ effekt

bull Tidligere meta‐analyse som viste effekt af Gem‐platin‐kombinationer nu insignifikant

efter inklusion af dette studium

ADVANCED DISEASE

Herrmann 2008

LOCALLY ADVANCED DISEASE

ADVANCED DISEASEADVANCED DISEASE

AdvancedAdvanced diseasedisease

bullbull Median Median survivalsurvival untreateduntreated 33--4 4 monthsmonthsbullbull PrimaryPrimary goalsgoals of of treatmenttreatment

ndashndash Prolongation of Prolongation of survivalsurvivalndashndash ImprovementImprovement in in QoLQoL

ADVANCED DISEASE

GemcitabineGemcitabine vs 5vs 5--FUFU

Burris H et al J Clin Oncol 1997152403-2413

Gemcitabine 5-FU P

Clinical benefit response 24 5 0002 Median survival (months) 57 44 0002 Time to progression (months) 21 09 0001 6-month survival 46 31 1-year survival 18 2 Partial response 54 0 Stable disease 393 19 Composite of measurements of pain (analgesic consumption and pain intensity) Karnofsky

performance status and weight

ADVANCED DISEASE

SurvivalSurvival of of GemGem--treatedtreated patients patients accordingaccording to performance statusto performance status

Storinolo et al Cancer 1998

ADVANCED DISEASE

Combination chemotherapyCombination chemotherapy GemGem--CapCap

JCO october 2009

ADVANCED DISEASE

CunninghamCunningham et al GEMet al GEM--CAPCAP

Hazard ratio 080 95 CI 065ndash098Log-rank p=0026

Eur J Cancer Suppl 2005

Interim analysis 2005Final analysis 2009

ADVANCED DISEASE

MetaMeta--analysisanalysis of GEMof GEM--CAPCAP

Cunningham et al JCO 2009

ADVANCED DISEASE

Gem vs Gem vs GemGem‐‐platinumplatinumDi Miao A randomized

trial

of gemcitabine

(G) versus G plus cisplatin

in chemotherapy‐naive

advanced

pancreatic

adenocarcinoma The GIP‐1 (Gruppo

Italiano Pancreasmdash

GOIMGISCADGOIRC)

study

ASCO 2009

Gemcitabin

som kontrol +

cisplatin

ugentlig 25mgm2N=201

Gemcitabin

ugentlig i 7 uger

2 ugers pause og dag 18 15 i

4 ugers cyklusN=199

400 pt

ADVANCED DISEASE

GemGem GemCisGemCis

OSOS11‐‐year year survivalsurvivalPFSPFS

AnAnaeligaeligmimiTrombocytopeniTrombocytopeni

83 mdr 83 mdr 340 340 39 mdr 39 mdr

39392929

72 mdr 72 mdr 307 307 38 mdr38 mdr

50505757

A randomized

trial

of gemcitabine

(G) versus G plus cisplatin

in chemotherapy‐naive

advanced

pancreatic

adenocarcinoma

The GIP‐1 (Gruppo

Italiano Pancreasmdash

GOIMGISCADGOIRC)

study

Di Miao

bull Alle endepunkter insignifikantebull Subgruppeanalyse

af PS 0 Signifikant negativ effekt

bull Tidligere meta‐analyse som viste effekt af Gem‐platin‐kombinationer nu insignifikant

efter inklusion af dette studium

ADVANCED DISEASE

ADVANCED DISEASEADVANCED DISEASE

AdvancedAdvanced diseasedisease

bullbull Median Median survivalsurvival untreateduntreated 33--4 4 monthsmonthsbullbull PrimaryPrimary goalsgoals of of treatmenttreatment

ndashndash Prolongation of Prolongation of survivalsurvivalndashndash ImprovementImprovement in in QoLQoL

ADVANCED DISEASE

GemcitabineGemcitabine vs 5vs 5--FUFU

Burris H et al J Clin Oncol 1997152403-2413

Gemcitabine 5-FU P

Clinical benefit response 24 5 0002 Median survival (months) 57 44 0002 Time to progression (months) 21 09 0001 6-month survival 46 31 1-year survival 18 2 Partial response 54 0 Stable disease 393 19 Composite of measurements of pain (analgesic consumption and pain intensity) Karnofsky

performance status and weight

ADVANCED DISEASE

SurvivalSurvival of of GemGem--treatedtreated patients patients accordingaccording to performance statusto performance status

Storinolo et al Cancer 1998

ADVANCED DISEASE

Combination chemotherapyCombination chemotherapy GemGem--CapCap

JCO october 2009

ADVANCED DISEASE

CunninghamCunningham et al GEMet al GEM--CAPCAP

Hazard ratio 080 95 CI 065ndash098Log-rank p=0026

Eur J Cancer Suppl 2005

Interim analysis 2005Final analysis 2009

ADVANCED DISEASE

MetaMeta--analysisanalysis of GEMof GEM--CAPCAP

Cunningham et al JCO 2009

ADVANCED DISEASE

Gem vs Gem vs GemGem‐‐platinumplatinumDi Miao A randomized

trial

of gemcitabine

(G) versus G plus cisplatin

in chemotherapy‐naive

advanced

pancreatic

adenocarcinoma The GIP‐1 (Gruppo

Italiano Pancreasmdash

GOIMGISCADGOIRC)

study

ASCO 2009

Gemcitabin

som kontrol +

cisplatin

ugentlig 25mgm2N=201

Gemcitabin

ugentlig i 7 uger

2 ugers pause og dag 18 15 i

4 ugers cyklusN=199

400 pt

ADVANCED DISEASE

GemGem GemCisGemCis

OSOS11‐‐year year survivalsurvivalPFSPFS

AnAnaeligaeligmimiTrombocytopeniTrombocytopeni

83 mdr 83 mdr 340 340 39 mdr 39 mdr

39392929

72 mdr 72 mdr 307 307 38 mdr38 mdr

50505757

A randomized

trial

of gemcitabine

(G) versus G plus cisplatin

in chemotherapy‐naive

advanced

pancreatic

adenocarcinoma

The GIP‐1 (Gruppo

Italiano Pancreasmdash

GOIMGISCADGOIRC)

study

Di Miao

bull Alle endepunkter insignifikantebull Subgruppeanalyse

af PS 0 Signifikant negativ effekt

bull Tidligere meta‐analyse som viste effekt af Gem‐platin‐kombinationer nu insignifikant

efter inklusion af dette studium

ADVANCED DISEASE

AdvancedAdvanced diseasedisease

bullbull Median Median survivalsurvival untreateduntreated 33--4 4 monthsmonthsbullbull PrimaryPrimary goalsgoals of of treatmenttreatment

ndashndash Prolongation of Prolongation of survivalsurvivalndashndash ImprovementImprovement in in QoLQoL

ADVANCED DISEASE

GemcitabineGemcitabine vs 5vs 5--FUFU

Burris H et al J Clin Oncol 1997152403-2413

Gemcitabine 5-FU P

Clinical benefit response 24 5 0002 Median survival (months) 57 44 0002 Time to progression (months) 21 09 0001 6-month survival 46 31 1-year survival 18 2 Partial response 54 0 Stable disease 393 19 Composite of measurements of pain (analgesic consumption and pain intensity) Karnofsky

performance status and weight

ADVANCED DISEASE

SurvivalSurvival of of GemGem--treatedtreated patients patients accordingaccording to performance statusto performance status

Storinolo et al Cancer 1998

ADVANCED DISEASE

Combination chemotherapyCombination chemotherapy GemGem--CapCap

JCO october 2009

ADVANCED DISEASE

CunninghamCunningham et al GEMet al GEM--CAPCAP

Hazard ratio 080 95 CI 065ndash098Log-rank p=0026

Eur J Cancer Suppl 2005

Interim analysis 2005Final analysis 2009

ADVANCED DISEASE

MetaMeta--analysisanalysis of GEMof GEM--CAPCAP

Cunningham et al JCO 2009

ADVANCED DISEASE

Gem vs Gem vs GemGem‐‐platinumplatinumDi Miao A randomized

trial

of gemcitabine

(G) versus G plus cisplatin

in chemotherapy‐naive

advanced

pancreatic

adenocarcinoma The GIP‐1 (Gruppo

Italiano Pancreasmdash

GOIMGISCADGOIRC)

study

ASCO 2009

Gemcitabin

som kontrol +

cisplatin

ugentlig 25mgm2N=201

Gemcitabin

ugentlig i 7 uger

2 ugers pause og dag 18 15 i

4 ugers cyklusN=199

400 pt

ADVANCED DISEASE

GemGem GemCisGemCis

OSOS11‐‐year year survivalsurvivalPFSPFS

AnAnaeligaeligmimiTrombocytopeniTrombocytopeni

83 mdr 83 mdr 340 340 39 mdr 39 mdr

39392929

72 mdr 72 mdr 307 307 38 mdr38 mdr

50505757

A randomized

trial

of gemcitabine

(G) versus G plus cisplatin

in chemotherapy‐naive

advanced

pancreatic

adenocarcinoma

The GIP‐1 (Gruppo

Italiano Pancreasmdash

GOIMGISCADGOIRC)

study

Di Miao

bull Alle endepunkter insignifikantebull Subgruppeanalyse

af PS 0 Signifikant negativ effekt

bull Tidligere meta‐analyse som viste effekt af Gem‐platin‐kombinationer nu insignifikant

efter inklusion af dette studium

ADVANCED DISEASE

GemcitabineGemcitabine vs 5vs 5--FUFU

Burris H et al J Clin Oncol 1997152403-2413

Gemcitabine 5-FU P

Clinical benefit response 24 5 0002 Median survival (months) 57 44 0002 Time to progression (months) 21 09 0001 6-month survival 46 31 1-year survival 18 2 Partial response 54 0 Stable disease 393 19 Composite of measurements of pain (analgesic consumption and pain intensity) Karnofsky

performance status and weight

ADVANCED DISEASE

SurvivalSurvival of of GemGem--treatedtreated patients patients accordingaccording to performance statusto performance status

Storinolo et al Cancer 1998

ADVANCED DISEASE

Combination chemotherapyCombination chemotherapy GemGem--CapCap

JCO october 2009

ADVANCED DISEASE

CunninghamCunningham et al GEMet al GEM--CAPCAP

Hazard ratio 080 95 CI 065ndash098Log-rank p=0026

Eur J Cancer Suppl 2005

Interim analysis 2005Final analysis 2009

ADVANCED DISEASE

MetaMeta--analysisanalysis of GEMof GEM--CAPCAP

Cunningham et al JCO 2009

ADVANCED DISEASE

Gem vs Gem vs GemGem‐‐platinumplatinumDi Miao A randomized

trial

of gemcitabine

(G) versus G plus cisplatin

in chemotherapy‐naive

advanced

pancreatic

adenocarcinoma The GIP‐1 (Gruppo

Italiano Pancreasmdash

GOIMGISCADGOIRC)

study

ASCO 2009

Gemcitabin

som kontrol +

cisplatin

ugentlig 25mgm2N=201

Gemcitabin

ugentlig i 7 uger

2 ugers pause og dag 18 15 i

4 ugers cyklusN=199

400 pt

ADVANCED DISEASE

GemGem GemCisGemCis

OSOS11‐‐year year survivalsurvivalPFSPFS

AnAnaeligaeligmimiTrombocytopeniTrombocytopeni

83 mdr 83 mdr 340 340 39 mdr 39 mdr

39392929

72 mdr 72 mdr 307 307 38 mdr38 mdr

50505757

A randomized

trial

of gemcitabine

(G) versus G plus cisplatin

in chemotherapy‐naive

advanced

pancreatic

adenocarcinoma

The GIP‐1 (Gruppo

Italiano Pancreasmdash

GOIMGISCADGOIRC)

study

Di Miao

bull Alle endepunkter insignifikantebull Subgruppeanalyse

af PS 0 Signifikant negativ effekt

bull Tidligere meta‐analyse som viste effekt af Gem‐platin‐kombinationer nu insignifikant

efter inklusion af dette studium

ADVANCED DISEASE

SurvivalSurvival of of GemGem--treatedtreated patients patients accordingaccording to performance statusto performance status

Storinolo et al Cancer 1998

ADVANCED DISEASE

Combination chemotherapyCombination chemotherapy GemGem--CapCap

JCO october 2009

ADVANCED DISEASE

CunninghamCunningham et al GEMet al GEM--CAPCAP

Hazard ratio 080 95 CI 065ndash098Log-rank p=0026

Eur J Cancer Suppl 2005

Interim analysis 2005Final analysis 2009

ADVANCED DISEASE

MetaMeta--analysisanalysis of GEMof GEM--CAPCAP

Cunningham et al JCO 2009

ADVANCED DISEASE

Gem vs Gem vs GemGem‐‐platinumplatinumDi Miao A randomized

trial

of gemcitabine

(G) versus G plus cisplatin

in chemotherapy‐naive

advanced

pancreatic

adenocarcinoma The GIP‐1 (Gruppo

Italiano Pancreasmdash

GOIMGISCADGOIRC)

study

ASCO 2009

Gemcitabin

som kontrol +

cisplatin

ugentlig 25mgm2N=201

Gemcitabin

ugentlig i 7 uger

2 ugers pause og dag 18 15 i

4 ugers cyklusN=199

400 pt

ADVANCED DISEASE

GemGem GemCisGemCis

OSOS11‐‐year year survivalsurvivalPFSPFS

AnAnaeligaeligmimiTrombocytopeniTrombocytopeni

83 mdr 83 mdr 340 340 39 mdr 39 mdr

39392929

72 mdr 72 mdr 307 307 38 mdr38 mdr

50505757

A randomized

trial

of gemcitabine

(G) versus G plus cisplatin

in chemotherapy‐naive

advanced

pancreatic

adenocarcinoma

The GIP‐1 (Gruppo

Italiano Pancreasmdash

GOIMGISCADGOIRC)

study

Di Miao

bull Alle endepunkter insignifikantebull Subgruppeanalyse

af PS 0 Signifikant negativ effekt

bull Tidligere meta‐analyse som viste effekt af Gem‐platin‐kombinationer nu insignifikant

efter inklusion af dette studium

ADVANCED DISEASE

Combination chemotherapyCombination chemotherapy GemGem--CapCap

JCO october 2009

ADVANCED DISEASE

CunninghamCunningham et al GEMet al GEM--CAPCAP

Hazard ratio 080 95 CI 065ndash098Log-rank p=0026

Eur J Cancer Suppl 2005

Interim analysis 2005Final analysis 2009

ADVANCED DISEASE

MetaMeta--analysisanalysis of GEMof GEM--CAPCAP

Cunningham et al JCO 2009

ADVANCED DISEASE

Gem vs Gem vs GemGem‐‐platinumplatinumDi Miao A randomized

trial

of gemcitabine

(G) versus G plus cisplatin

in chemotherapy‐naive

advanced

pancreatic

adenocarcinoma The GIP‐1 (Gruppo

Italiano Pancreasmdash

GOIMGISCADGOIRC)

study

ASCO 2009

Gemcitabin

som kontrol +

cisplatin

ugentlig 25mgm2N=201

Gemcitabin

ugentlig i 7 uger

2 ugers pause og dag 18 15 i

4 ugers cyklusN=199

400 pt

ADVANCED DISEASE

GemGem GemCisGemCis

OSOS11‐‐year year survivalsurvivalPFSPFS

AnAnaeligaeligmimiTrombocytopeniTrombocytopeni

83 mdr 83 mdr 340 340 39 mdr 39 mdr

39392929

72 mdr 72 mdr 307 307 38 mdr38 mdr

50505757

A randomized

trial

of gemcitabine

(G) versus G plus cisplatin

in chemotherapy‐naive

advanced

pancreatic

adenocarcinoma

The GIP‐1 (Gruppo

Italiano Pancreasmdash

GOIMGISCADGOIRC)

study

Di Miao

bull Alle endepunkter insignifikantebull Subgruppeanalyse

af PS 0 Signifikant negativ effekt

bull Tidligere meta‐analyse som viste effekt af Gem‐platin‐kombinationer nu insignifikant

efter inklusion af dette studium

ADVANCED DISEASE

CunninghamCunningham et al GEMet al GEM--CAPCAP

Hazard ratio 080 95 CI 065ndash098Log-rank p=0026

Eur J Cancer Suppl 2005

Interim analysis 2005Final analysis 2009

ADVANCED DISEASE

MetaMeta--analysisanalysis of GEMof GEM--CAPCAP

Cunningham et al JCO 2009

ADVANCED DISEASE

Gem vs Gem vs GemGem‐‐platinumplatinumDi Miao A randomized

trial

of gemcitabine

(G) versus G plus cisplatin

in chemotherapy‐naive

advanced

pancreatic

adenocarcinoma The GIP‐1 (Gruppo

Italiano Pancreasmdash

GOIMGISCADGOIRC)

study

ASCO 2009

Gemcitabin

som kontrol +

cisplatin

ugentlig 25mgm2N=201

Gemcitabin

ugentlig i 7 uger

2 ugers pause og dag 18 15 i

4 ugers cyklusN=199

400 pt

ADVANCED DISEASE

GemGem GemCisGemCis

OSOS11‐‐year year survivalsurvivalPFSPFS

AnAnaeligaeligmimiTrombocytopeniTrombocytopeni

83 mdr 83 mdr 340 340 39 mdr 39 mdr

39392929

72 mdr 72 mdr 307 307 38 mdr38 mdr

50505757

A randomized

trial

of gemcitabine

(G) versus G plus cisplatin

in chemotherapy‐naive

advanced

pancreatic

adenocarcinoma

The GIP‐1 (Gruppo

Italiano Pancreasmdash

GOIMGISCADGOIRC)

study

Di Miao

bull Alle endepunkter insignifikantebull Subgruppeanalyse

af PS 0 Signifikant negativ effekt

bull Tidligere meta‐analyse som viste effekt af Gem‐platin‐kombinationer nu insignifikant

efter inklusion af dette studium

ADVANCED DISEASE

MetaMeta--analysisanalysis of GEMof GEM--CAPCAP

Cunningham et al JCO 2009

ADVANCED DISEASE

Gem vs Gem vs GemGem‐‐platinumplatinumDi Miao A randomized

trial

of gemcitabine

(G) versus G plus cisplatin

in chemotherapy‐naive

advanced

pancreatic

adenocarcinoma The GIP‐1 (Gruppo

Italiano Pancreasmdash

GOIMGISCADGOIRC)

study

ASCO 2009

Gemcitabin

som kontrol +

cisplatin

ugentlig 25mgm2N=201

Gemcitabin

ugentlig i 7 uger

2 ugers pause og dag 18 15 i

4 ugers cyklusN=199

400 pt

ADVANCED DISEASE

GemGem GemCisGemCis

OSOS11‐‐year year survivalsurvivalPFSPFS

AnAnaeligaeligmimiTrombocytopeniTrombocytopeni

83 mdr 83 mdr 340 340 39 mdr 39 mdr

39392929

72 mdr 72 mdr 307 307 38 mdr38 mdr

50505757

A randomized

trial

of gemcitabine

(G) versus G plus cisplatin

in chemotherapy‐naive

advanced

pancreatic

adenocarcinoma

The GIP‐1 (Gruppo

Italiano Pancreasmdash

GOIMGISCADGOIRC)

study

Di Miao

bull Alle endepunkter insignifikantebull Subgruppeanalyse

af PS 0 Signifikant negativ effekt

bull Tidligere meta‐analyse som viste effekt af Gem‐platin‐kombinationer nu insignifikant

efter inklusion af dette studium

ADVANCED DISEASE

Gem vs Gem vs GemGem‐‐platinumplatinumDi Miao A randomized

trial

of gemcitabine

(G) versus G plus cisplatin

in chemotherapy‐naive

advanced

pancreatic

adenocarcinoma The GIP‐1 (Gruppo

Italiano Pancreasmdash

GOIMGISCADGOIRC)

study

ASCO 2009

Gemcitabin

som kontrol +

cisplatin

ugentlig 25mgm2N=201

Gemcitabin

ugentlig i 7 uger

2 ugers pause og dag 18 15 i

4 ugers cyklusN=199

400 pt

ADVANCED DISEASE

GemGem GemCisGemCis

OSOS11‐‐year year survivalsurvivalPFSPFS

AnAnaeligaeligmimiTrombocytopeniTrombocytopeni

83 mdr 83 mdr 340 340 39 mdr 39 mdr

39392929

72 mdr 72 mdr 307 307 38 mdr38 mdr

50505757

A randomized

trial

of gemcitabine

(G) versus G plus cisplatin

in chemotherapy‐naive

advanced

pancreatic

adenocarcinoma

The GIP‐1 (Gruppo

Italiano Pancreasmdash

GOIMGISCADGOIRC)

study

Di Miao

bull Alle endepunkter insignifikantebull Subgruppeanalyse

af PS 0 Signifikant negativ effekt

bull Tidligere meta‐analyse som viste effekt af Gem‐platin‐kombinationer nu insignifikant

efter inklusion af dette studium

ADVANCED DISEASE

GemGem GemCisGemCis

OSOS11‐‐year year survivalsurvivalPFSPFS

AnAnaeligaeligmimiTrombocytopeniTrombocytopeni

83 mdr 83 mdr 340 340 39 mdr 39 mdr

39392929

72 mdr 72 mdr 307 307 38 mdr38 mdr

50505757

A randomized

trial

of gemcitabine

(G) versus G plus cisplatin

in chemotherapy‐naive

advanced

pancreatic

adenocarcinoma

The GIP‐1 (Gruppo

Italiano Pancreasmdash

GOIMGISCADGOIRC)

study

Di Miao

bull Alle endepunkter insignifikantebull Subgruppeanalyse

af PS 0 Signifikant negativ effekt

bull Tidligere meta‐analyse som viste effekt af Gem‐platin‐kombinationer nu insignifikant

efter inklusion af dette studium

ADVANCED DISEASE

CombinationCombination chemotherapychemotherapy and and effecteffect accordingaccording to to performance statusperformance status

Heinemann et al BMC Cancer 2008

ADVANCED DISEASE

PA3 study GemPA3 study Gem--erlotiniberlotinib Overall survivalOverall survival

10090807060504030201

0

Surv

ival

pro

babi

lity

0 6 12 18 24Survival (months)

Tarcevatrade gemcitabine

(n=285)

Placebo gemcitabine

(n=284)

Median survival (months) 637 591

1-year survival 24 17

HR=079 (95 CI 066-095) P=0011 (adjusted for PS and extent of disease at randomization)

TarcevaTM + gemcitabinePlacebo + gemcitabine

Moore et al JCO 2007

ADVANCED DISEASE

PA3 studyPA3 study Hazard ratios for survivalHazard ratios for survival

HR 95 CI n

Tarcevaplacebo

Performance status 0-1Performance status 2

Locally advancedDistant metastasis

Pain 20 Pain gt20

MaleFemale

Age lt65Age 65

United StatesCanada

Rest of World

HER1EGFR positiveHER1EGFR negative

HER1EGFR unknown

1

082 07-10 569

087 07-11 463056 04-08 106

094 06-14 138078 06-09 431

070 05-09 258098 08-13 296

074 06-09 298096 07-13 271

074 06-10 301093 07-12 268

071 05-09 211079 05-12 117096 07-13 241

073 04-12 74077 05-13 71086 07-11 424

Fact

ors

Moore et al JCO 2007

ADVANCED DISEASE

Events

Tarceva () n=282

Placebo () n=280

Any Grade 34 Any Grade 34Rash 72 6 29 1Diarrhoea 56 6 41 2Infection 43 17 34 16Stomatitis 23 lt1 14 0Pneumonitis 2 2 1 lt1Fatigue 89 15 86 15

PA3 studyPA3 study Adverse eventsAdverse events

Moore et al JCO 2007

ADVANCED DISEASE

AccetableAccetable standard standard systemicsystemic treatmenttreatment options 2009options 2009

bullbull GEM GEM alonealonebullbull GEMGEM--erlotiniberlotinib

ndashndash registredregistred for for metastaticmetastatic PC PC onlyonly mOSmOS + 12 + 12 daysdays somesome additionaladditional toxicitytoxicity

bullbull GEMGEM--CAP CAP mOSmOS + 1 + 1 monthmonth onlyonly significantsignificant in in metameta--analysisanalysis

bullbull GEMGEM--platinumplatinum ndashndash doubtfuldoubtful effecteffect -- nownow not not significantsignificant in in metameta--

analysisanalysis significantsignificant toxicitytoxicity

ADVANCED DISEASE

SUPPORTIVE CARESUPPORTIVE CARE

Forebyggelse af venForebyggelse af venoslashoslashse se tromboembolisketromboemboliske events (VTE) ved events (VTE) ved pancreascancerpancreascancer

SUPPORTIVE CARE

GONKO 004 GONKO 004 trialtrialA prospective randomized trial of chemotherapy with or without the low molecular weight heparin (LMWH)

enoxaparin in patients (pts) with advanced pancreatic cancer (APC) Results of the CONKO 004 trial HReiss et al ASCO 2009

Baggrund

VTE forekommer hos ca 10 af patienter med PC

Formaringl

Undersoslashge effekt af LMWH (Klexane) i kombination med

kemoterapi mht frekvens af VTE og mOS

Inklusion

Avanceret PC ikke tidligere kemoterapi

Karnofsky

PS gt 60

Ingen stoslashrre bloslashdning indenfor 2 uger ingen VTE indenfor

2 aringr

SUPPORTIVE CARE

A prospective randomized trial of chemotherapy with or without the low molecular weight heparin (LMWH) enoxaparin in patients (pts) with advanced pancreatic cancer (APC) Results of the CONKO 004 trial HReiss et

al ASCO 2009

Antal af VTE 15152 i observation ndash 2160 i LMWH

SUPPORTIVE CARE

A prospective randomized trial of chemotherapy with or without the low molecular weight heparin (LMWH) enoxaparin in patients (pts) with advanced pancreatic cancer (APC) Results of the CONKO 004 trial HReiss et

al

Konklusion

LMWH er effektiv og sikker behandling til forebyggelse af

VTE hos patienter med pancreascancer

Endelige resultater paring

mOS og mTTP

afventes

SUPPORTIVE CARE

TreatmentTreatment of of malignantmalignant ascitesascites

SUPPORTIVE CARE

HeissHeiss M et al M et al CatumaxomabCatumaxomab ndashndash a new treatment option for patients a new treatment option for patients with malignant with malignant ascitesascites Ann Oncol20Suppl 7 2009 Ann Oncol20Suppl 7 2009

bullbull CatumaxomabCatumaxomab TrifunctionalTrifunctional antibody 4 antibody 4 infusions infusions ipip over 6 h in ascending doses over 6 h in ascending doses

bullbull Multicenter randomized openMulticenter randomized open--label phase label phase IIIII studyIIIII study

bullbull 258 pts with symptomatic malignant 258 pts with symptomatic malignant ascitesascites due to epithelial cancerdue to epithelial cancer

SUPPORTIVE CARE

HeissHeiss M et al M et al CatumaxomabCatumaxomab ndashndash a new treatment option for patients a new treatment option for patients with malignant with malignant ascitesascites Ann Oncol20Suppl 7 2009 Ann Oncol20Suppl 7 2009

bullbull Subgroup analysis of 129 Subgroup analysis of 129 ovarian and 129 nonovarian and 129 non-- ovarian (gastric pancreatic ovarian (gastric pancreatic CRC etc) cancer patients CRC etc) cancer patients randomizedrandomized

bullbull AEsAEs Cytokine release Cytokine release related symptoms in 80 related symptoms in 80 mostly shortmostly short--lasting and of lasting and of grade 1grade 1--22

SUPPORTIVE CARE

0

10

20

30

40

50

60

Non-ovariancancer

Ovariancancer

CatumaxomabPlacebo

Median puncture-free survival (days)

2p lt 00001

Pancreatic islet cell Pancreatic islet cell tumourstumours

Pancreatic NET

Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009

bullbull SunitinibSunitinib Oral Oral multitargetedmultitargeted tyrosine tyrosine kinasekinase inhibitor used for inhibitor used for mRCCmRCC and GISTand GIST

bullbull Phase IIPhase II--study of study of sunitinibsunitinib in NETin NET11 ORR ORR of 167 in 66 pts with of 167 in 66 pts with pNETpNET

1) Kulke MH et al JCO 263403-10 2008

Pancreatic NET

Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009

bullbull Local locally advanced or metastatic Local locally advanced or metastatic wellwell--differentiated differentiated pNETpNET not amenable to not amenable to curative therapy and with disease curative therapy and with disease progression in the prior 12 monthsprogression in the prior 12 months

bullbull Primary end point PFSPrimary end point PFSbullbull SunitinibSunitinib 375 mgday or placebo375 mgday or placebo

Pancreatic NET

Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009

bullbull 154 pts randomized154 pts randomizedbullbull Toxicity events Toxicity events sunitinibsunitinib

ndashndash Diarrhea nausea vomiting asthenia fatigueDiarrhea nausea vomiting asthenia fatiguendashndash Grade 3Grade 3--4 4 neutropenianeutropenia (12) hypertension (12) hypertension

(9) diarrhea (7) hypoglycemia (7) (9) diarrhea (7) hypoglycemia (7) palmarpalmar--plantar plantar erythrodysesthesiaerythrodysesthesia (7)(7)

Pancreatic NET

Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009

bullbull Interim analysis with Interim analysis with 73 events73 eventsndashndash 5 deaths in 5 deaths in sunitinibsunitinib

arm arm vsvs 15 in placebo 15 in placebo armarm

bullbull Study halted early Study halted early and patients on and patients on placebo given the placebo given the opportunity to cross opportunity to cross over to over to sunitinibsunitinib

Pancreatic NET

0

2

4

6

8

10

12

Medianprogressionfree survival

(months)

PlaceboSunitinib

HR 0397 2p lt0001

PA3 study GemPA3 study Gem--erlotiniberlotinib Overall survivalOverall survival

10090807060504030201

0

Surv

ival

pro

babi

lity

0 6 12 18 24Survival (months)

Tarcevatrade gemcitabine

(n=285)

Placebo gemcitabine

(n=284)

Median survival (months) 637 591

1-year survival 24 17

HR=079 (95 CI 066-095) P=0011 (adjusted for PS and extent of disease at randomization)

TarcevaTM + gemcitabinePlacebo + gemcitabine

Moore et al JCO 2007

ADVANCED DISEASE

PA3 studyPA3 study Hazard ratios for survivalHazard ratios for survival

HR 95 CI n

Tarcevaplacebo

Performance status 0-1Performance status 2

Locally advancedDistant metastasis

Pain 20 Pain gt20

MaleFemale

Age lt65Age 65

United StatesCanada

Rest of World

HER1EGFR positiveHER1EGFR negative

HER1EGFR unknown

1

082 07-10 569

087 07-11 463056 04-08 106

094 06-14 138078 06-09 431

070 05-09 258098 08-13 296

074 06-09 298096 07-13 271

074 06-10 301093 07-12 268

071 05-09 211079 05-12 117096 07-13 241

073 04-12 74077 05-13 71086 07-11 424

Fact

ors

Moore et al JCO 2007

ADVANCED DISEASE

Events

Tarceva () n=282

Placebo () n=280

Any Grade 34 Any Grade 34Rash 72 6 29 1Diarrhoea 56 6 41 2Infection 43 17 34 16Stomatitis 23 lt1 14 0Pneumonitis 2 2 1 lt1Fatigue 89 15 86 15

PA3 studyPA3 study Adverse eventsAdverse events

Moore et al JCO 2007

ADVANCED DISEASE

AccetableAccetable standard standard systemicsystemic treatmenttreatment options 2009options 2009

bullbull GEM GEM alonealonebullbull GEMGEM--erlotiniberlotinib

ndashndash registredregistred for for metastaticmetastatic PC PC onlyonly mOSmOS + 12 + 12 daysdays somesome additionaladditional toxicitytoxicity

bullbull GEMGEM--CAP CAP mOSmOS + 1 + 1 monthmonth onlyonly significantsignificant in in metameta--analysisanalysis

bullbull GEMGEM--platinumplatinum ndashndash doubtfuldoubtful effecteffect -- nownow not not significantsignificant in in metameta--

analysisanalysis significantsignificant toxicitytoxicity

ADVANCED DISEASE

SUPPORTIVE CARESUPPORTIVE CARE

Forebyggelse af venForebyggelse af venoslashoslashse se tromboembolisketromboemboliske events (VTE) ved events (VTE) ved pancreascancerpancreascancer

SUPPORTIVE CARE

GONKO 004 GONKO 004 trialtrialA prospective randomized trial of chemotherapy with or without the low molecular weight heparin (LMWH)

enoxaparin in patients (pts) with advanced pancreatic cancer (APC) Results of the CONKO 004 trial HReiss et al ASCO 2009

Baggrund

VTE forekommer hos ca 10 af patienter med PC

Formaringl

Undersoslashge effekt af LMWH (Klexane) i kombination med

kemoterapi mht frekvens af VTE og mOS

Inklusion

Avanceret PC ikke tidligere kemoterapi

Karnofsky

PS gt 60

Ingen stoslashrre bloslashdning indenfor 2 uger ingen VTE indenfor

2 aringr

SUPPORTIVE CARE

A prospective randomized trial of chemotherapy with or without the low molecular weight heparin (LMWH) enoxaparin in patients (pts) with advanced pancreatic cancer (APC) Results of the CONKO 004 trial HReiss et

al ASCO 2009

Antal af VTE 15152 i observation ndash 2160 i LMWH

SUPPORTIVE CARE

A prospective randomized trial of chemotherapy with or without the low molecular weight heparin (LMWH) enoxaparin in patients (pts) with advanced pancreatic cancer (APC) Results of the CONKO 004 trial HReiss et

al

Konklusion

LMWH er effektiv og sikker behandling til forebyggelse af

VTE hos patienter med pancreascancer

Endelige resultater paring

mOS og mTTP

afventes

SUPPORTIVE CARE

TreatmentTreatment of of malignantmalignant ascitesascites

SUPPORTIVE CARE

HeissHeiss M et al M et al CatumaxomabCatumaxomab ndashndash a new treatment option for patients a new treatment option for patients with malignant with malignant ascitesascites Ann Oncol20Suppl 7 2009 Ann Oncol20Suppl 7 2009

bullbull CatumaxomabCatumaxomab TrifunctionalTrifunctional antibody 4 antibody 4 infusions infusions ipip over 6 h in ascending doses over 6 h in ascending doses

bullbull Multicenter randomized openMulticenter randomized open--label phase label phase IIIII studyIIIII study

bullbull 258 pts with symptomatic malignant 258 pts with symptomatic malignant ascitesascites due to epithelial cancerdue to epithelial cancer

SUPPORTIVE CARE

HeissHeiss M et al M et al CatumaxomabCatumaxomab ndashndash a new treatment option for patients a new treatment option for patients with malignant with malignant ascitesascites Ann Oncol20Suppl 7 2009 Ann Oncol20Suppl 7 2009

bullbull Subgroup analysis of 129 Subgroup analysis of 129 ovarian and 129 nonovarian and 129 non-- ovarian (gastric pancreatic ovarian (gastric pancreatic CRC etc) cancer patients CRC etc) cancer patients randomizedrandomized

bullbull AEsAEs Cytokine release Cytokine release related symptoms in 80 related symptoms in 80 mostly shortmostly short--lasting and of lasting and of grade 1grade 1--22

SUPPORTIVE CARE

0

10

20

30

40

50

60

Non-ovariancancer

Ovariancancer

CatumaxomabPlacebo

Median puncture-free survival (days)

2p lt 00001

Pancreatic islet cell Pancreatic islet cell tumourstumours

Pancreatic NET

Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009

bullbull SunitinibSunitinib Oral Oral multitargetedmultitargeted tyrosine tyrosine kinasekinase inhibitor used for inhibitor used for mRCCmRCC and GISTand GIST

bullbull Phase IIPhase II--study of study of sunitinibsunitinib in NETin NET11 ORR ORR of 167 in 66 pts with of 167 in 66 pts with pNETpNET

1) Kulke MH et al JCO 263403-10 2008

Pancreatic NET

Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009

bullbull Local locally advanced or metastatic Local locally advanced or metastatic wellwell--differentiated differentiated pNETpNET not amenable to not amenable to curative therapy and with disease curative therapy and with disease progression in the prior 12 monthsprogression in the prior 12 months

bullbull Primary end point PFSPrimary end point PFSbullbull SunitinibSunitinib 375 mgday or placebo375 mgday or placebo

Pancreatic NET

Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009

bullbull 154 pts randomized154 pts randomizedbullbull Toxicity events Toxicity events sunitinibsunitinib

ndashndash Diarrhea nausea vomiting asthenia fatigueDiarrhea nausea vomiting asthenia fatiguendashndash Grade 3Grade 3--4 4 neutropenianeutropenia (12) hypertension (12) hypertension

(9) diarrhea (7) hypoglycemia (7) (9) diarrhea (7) hypoglycemia (7) palmarpalmar--plantar plantar erythrodysesthesiaerythrodysesthesia (7)(7)

Pancreatic NET

Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009

bullbull Interim analysis with Interim analysis with 73 events73 eventsndashndash 5 deaths in 5 deaths in sunitinibsunitinib

arm arm vsvs 15 in placebo 15 in placebo armarm

bullbull Study halted early Study halted early and patients on and patients on placebo given the placebo given the opportunity to cross opportunity to cross over to over to sunitinibsunitinib

Pancreatic NET

0

2

4

6

8

10

12

Medianprogressionfree survival

(months)

PlaceboSunitinib

HR 0397 2p lt0001

PA3 studyPA3 study Hazard ratios for survivalHazard ratios for survival

HR 95 CI n

Tarcevaplacebo

Performance status 0-1Performance status 2

Locally advancedDistant metastasis

Pain 20 Pain gt20

MaleFemale

Age lt65Age 65

United StatesCanada

Rest of World

HER1EGFR positiveHER1EGFR negative

HER1EGFR unknown

1

082 07-10 569

087 07-11 463056 04-08 106

094 06-14 138078 06-09 431

070 05-09 258098 08-13 296

074 06-09 298096 07-13 271

074 06-10 301093 07-12 268

071 05-09 211079 05-12 117096 07-13 241

073 04-12 74077 05-13 71086 07-11 424

Fact

ors

Moore et al JCO 2007

ADVANCED DISEASE

Events

Tarceva () n=282

Placebo () n=280

Any Grade 34 Any Grade 34Rash 72 6 29 1Diarrhoea 56 6 41 2Infection 43 17 34 16Stomatitis 23 lt1 14 0Pneumonitis 2 2 1 lt1Fatigue 89 15 86 15

PA3 studyPA3 study Adverse eventsAdverse events

Moore et al JCO 2007

ADVANCED DISEASE

AccetableAccetable standard standard systemicsystemic treatmenttreatment options 2009options 2009

bullbull GEM GEM alonealonebullbull GEMGEM--erlotiniberlotinib

ndashndash registredregistred for for metastaticmetastatic PC PC onlyonly mOSmOS + 12 + 12 daysdays somesome additionaladditional toxicitytoxicity

bullbull GEMGEM--CAP CAP mOSmOS + 1 + 1 monthmonth onlyonly significantsignificant in in metameta--analysisanalysis

bullbull GEMGEM--platinumplatinum ndashndash doubtfuldoubtful effecteffect -- nownow not not significantsignificant in in metameta--

analysisanalysis significantsignificant toxicitytoxicity

ADVANCED DISEASE

SUPPORTIVE CARESUPPORTIVE CARE

Forebyggelse af venForebyggelse af venoslashoslashse se tromboembolisketromboemboliske events (VTE) ved events (VTE) ved pancreascancerpancreascancer

SUPPORTIVE CARE

GONKO 004 GONKO 004 trialtrialA prospective randomized trial of chemotherapy with or without the low molecular weight heparin (LMWH)

enoxaparin in patients (pts) with advanced pancreatic cancer (APC) Results of the CONKO 004 trial HReiss et al ASCO 2009

Baggrund

VTE forekommer hos ca 10 af patienter med PC

Formaringl

Undersoslashge effekt af LMWH (Klexane) i kombination med

kemoterapi mht frekvens af VTE og mOS

Inklusion

Avanceret PC ikke tidligere kemoterapi

Karnofsky

PS gt 60

Ingen stoslashrre bloslashdning indenfor 2 uger ingen VTE indenfor

2 aringr

SUPPORTIVE CARE

A prospective randomized trial of chemotherapy with or without the low molecular weight heparin (LMWH) enoxaparin in patients (pts) with advanced pancreatic cancer (APC) Results of the CONKO 004 trial HReiss et

al ASCO 2009

Antal af VTE 15152 i observation ndash 2160 i LMWH

SUPPORTIVE CARE

A prospective randomized trial of chemotherapy with or without the low molecular weight heparin (LMWH) enoxaparin in patients (pts) with advanced pancreatic cancer (APC) Results of the CONKO 004 trial HReiss et

al

Konklusion

LMWH er effektiv og sikker behandling til forebyggelse af

VTE hos patienter med pancreascancer

Endelige resultater paring

mOS og mTTP

afventes

SUPPORTIVE CARE

TreatmentTreatment of of malignantmalignant ascitesascites

SUPPORTIVE CARE

HeissHeiss M et al M et al CatumaxomabCatumaxomab ndashndash a new treatment option for patients a new treatment option for patients with malignant with malignant ascitesascites Ann Oncol20Suppl 7 2009 Ann Oncol20Suppl 7 2009

bullbull CatumaxomabCatumaxomab TrifunctionalTrifunctional antibody 4 antibody 4 infusions infusions ipip over 6 h in ascending doses over 6 h in ascending doses

bullbull Multicenter randomized openMulticenter randomized open--label phase label phase IIIII studyIIIII study

bullbull 258 pts with symptomatic malignant 258 pts with symptomatic malignant ascitesascites due to epithelial cancerdue to epithelial cancer

SUPPORTIVE CARE

HeissHeiss M et al M et al CatumaxomabCatumaxomab ndashndash a new treatment option for patients a new treatment option for patients with malignant with malignant ascitesascites Ann Oncol20Suppl 7 2009 Ann Oncol20Suppl 7 2009

bullbull Subgroup analysis of 129 Subgroup analysis of 129 ovarian and 129 nonovarian and 129 non-- ovarian (gastric pancreatic ovarian (gastric pancreatic CRC etc) cancer patients CRC etc) cancer patients randomizedrandomized

bullbull AEsAEs Cytokine release Cytokine release related symptoms in 80 related symptoms in 80 mostly shortmostly short--lasting and of lasting and of grade 1grade 1--22

SUPPORTIVE CARE

0

10

20

30

40

50

60

Non-ovariancancer

Ovariancancer

CatumaxomabPlacebo

Median puncture-free survival (days)

2p lt 00001

Pancreatic islet cell Pancreatic islet cell tumourstumours

Pancreatic NET

Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009

bullbull SunitinibSunitinib Oral Oral multitargetedmultitargeted tyrosine tyrosine kinasekinase inhibitor used for inhibitor used for mRCCmRCC and GISTand GIST

bullbull Phase IIPhase II--study of study of sunitinibsunitinib in NETin NET11 ORR ORR of 167 in 66 pts with of 167 in 66 pts with pNETpNET

1) Kulke MH et al JCO 263403-10 2008

Pancreatic NET

Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009

bullbull Local locally advanced or metastatic Local locally advanced or metastatic wellwell--differentiated differentiated pNETpNET not amenable to not amenable to curative therapy and with disease curative therapy and with disease progression in the prior 12 monthsprogression in the prior 12 months

bullbull Primary end point PFSPrimary end point PFSbullbull SunitinibSunitinib 375 mgday or placebo375 mgday or placebo

Pancreatic NET

Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009

bullbull 154 pts randomized154 pts randomizedbullbull Toxicity events Toxicity events sunitinibsunitinib

ndashndash Diarrhea nausea vomiting asthenia fatigueDiarrhea nausea vomiting asthenia fatiguendashndash Grade 3Grade 3--4 4 neutropenianeutropenia (12) hypertension (12) hypertension

(9) diarrhea (7) hypoglycemia (7) (9) diarrhea (7) hypoglycemia (7) palmarpalmar--plantar plantar erythrodysesthesiaerythrodysesthesia (7)(7)

Pancreatic NET

Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009

bullbull Interim analysis with Interim analysis with 73 events73 eventsndashndash 5 deaths in 5 deaths in sunitinibsunitinib

arm arm vsvs 15 in placebo 15 in placebo armarm

bullbull Study halted early Study halted early and patients on and patients on placebo given the placebo given the opportunity to cross opportunity to cross over to over to sunitinibsunitinib

Pancreatic NET

0

2

4

6

8

10

12

Medianprogressionfree survival

(months)

PlaceboSunitinib

HR 0397 2p lt0001

Events

Tarceva () n=282

Placebo () n=280

Any Grade 34 Any Grade 34Rash 72 6 29 1Diarrhoea 56 6 41 2Infection 43 17 34 16Stomatitis 23 lt1 14 0Pneumonitis 2 2 1 lt1Fatigue 89 15 86 15

PA3 studyPA3 study Adverse eventsAdverse events

Moore et al JCO 2007

ADVANCED DISEASE

AccetableAccetable standard standard systemicsystemic treatmenttreatment options 2009options 2009

bullbull GEM GEM alonealonebullbull GEMGEM--erlotiniberlotinib

ndashndash registredregistred for for metastaticmetastatic PC PC onlyonly mOSmOS + 12 + 12 daysdays somesome additionaladditional toxicitytoxicity

bullbull GEMGEM--CAP CAP mOSmOS + 1 + 1 monthmonth onlyonly significantsignificant in in metameta--analysisanalysis

bullbull GEMGEM--platinumplatinum ndashndash doubtfuldoubtful effecteffect -- nownow not not significantsignificant in in metameta--

analysisanalysis significantsignificant toxicitytoxicity

ADVANCED DISEASE

SUPPORTIVE CARESUPPORTIVE CARE

Forebyggelse af venForebyggelse af venoslashoslashse se tromboembolisketromboemboliske events (VTE) ved events (VTE) ved pancreascancerpancreascancer

SUPPORTIVE CARE

GONKO 004 GONKO 004 trialtrialA prospective randomized trial of chemotherapy with or without the low molecular weight heparin (LMWH)

enoxaparin in patients (pts) with advanced pancreatic cancer (APC) Results of the CONKO 004 trial HReiss et al ASCO 2009

Baggrund

VTE forekommer hos ca 10 af patienter med PC

Formaringl

Undersoslashge effekt af LMWH (Klexane) i kombination med

kemoterapi mht frekvens af VTE og mOS

Inklusion

Avanceret PC ikke tidligere kemoterapi

Karnofsky

PS gt 60

Ingen stoslashrre bloslashdning indenfor 2 uger ingen VTE indenfor

2 aringr

SUPPORTIVE CARE

A prospective randomized trial of chemotherapy with or without the low molecular weight heparin (LMWH) enoxaparin in patients (pts) with advanced pancreatic cancer (APC) Results of the CONKO 004 trial HReiss et

al ASCO 2009

Antal af VTE 15152 i observation ndash 2160 i LMWH

SUPPORTIVE CARE

A prospective randomized trial of chemotherapy with or without the low molecular weight heparin (LMWH) enoxaparin in patients (pts) with advanced pancreatic cancer (APC) Results of the CONKO 004 trial HReiss et

al

Konklusion

LMWH er effektiv og sikker behandling til forebyggelse af

VTE hos patienter med pancreascancer

Endelige resultater paring

mOS og mTTP

afventes

SUPPORTIVE CARE

TreatmentTreatment of of malignantmalignant ascitesascites

SUPPORTIVE CARE

HeissHeiss M et al M et al CatumaxomabCatumaxomab ndashndash a new treatment option for patients a new treatment option for patients with malignant with malignant ascitesascites Ann Oncol20Suppl 7 2009 Ann Oncol20Suppl 7 2009

bullbull CatumaxomabCatumaxomab TrifunctionalTrifunctional antibody 4 antibody 4 infusions infusions ipip over 6 h in ascending doses over 6 h in ascending doses

bullbull Multicenter randomized openMulticenter randomized open--label phase label phase IIIII studyIIIII study

bullbull 258 pts with symptomatic malignant 258 pts with symptomatic malignant ascitesascites due to epithelial cancerdue to epithelial cancer

SUPPORTIVE CARE

HeissHeiss M et al M et al CatumaxomabCatumaxomab ndashndash a new treatment option for patients a new treatment option for patients with malignant with malignant ascitesascites Ann Oncol20Suppl 7 2009 Ann Oncol20Suppl 7 2009

bullbull Subgroup analysis of 129 Subgroup analysis of 129 ovarian and 129 nonovarian and 129 non-- ovarian (gastric pancreatic ovarian (gastric pancreatic CRC etc) cancer patients CRC etc) cancer patients randomizedrandomized

bullbull AEsAEs Cytokine release Cytokine release related symptoms in 80 related symptoms in 80 mostly shortmostly short--lasting and of lasting and of grade 1grade 1--22

SUPPORTIVE CARE

0

10

20

30

40

50

60

Non-ovariancancer

Ovariancancer

CatumaxomabPlacebo

Median puncture-free survival (days)

2p lt 00001

Pancreatic islet cell Pancreatic islet cell tumourstumours

Pancreatic NET

Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009

bullbull SunitinibSunitinib Oral Oral multitargetedmultitargeted tyrosine tyrosine kinasekinase inhibitor used for inhibitor used for mRCCmRCC and GISTand GIST

bullbull Phase IIPhase II--study of study of sunitinibsunitinib in NETin NET11 ORR ORR of 167 in 66 pts with of 167 in 66 pts with pNETpNET

1) Kulke MH et al JCO 263403-10 2008

Pancreatic NET

Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009

bullbull Local locally advanced or metastatic Local locally advanced or metastatic wellwell--differentiated differentiated pNETpNET not amenable to not amenable to curative therapy and with disease curative therapy and with disease progression in the prior 12 monthsprogression in the prior 12 months

bullbull Primary end point PFSPrimary end point PFSbullbull SunitinibSunitinib 375 mgday or placebo375 mgday or placebo

Pancreatic NET

Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009

bullbull 154 pts randomized154 pts randomizedbullbull Toxicity events Toxicity events sunitinibsunitinib

ndashndash Diarrhea nausea vomiting asthenia fatigueDiarrhea nausea vomiting asthenia fatiguendashndash Grade 3Grade 3--4 4 neutropenianeutropenia (12) hypertension (12) hypertension

(9) diarrhea (7) hypoglycemia (7) (9) diarrhea (7) hypoglycemia (7) palmarpalmar--plantar plantar erythrodysesthesiaerythrodysesthesia (7)(7)

Pancreatic NET

Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009

bullbull Interim analysis with Interim analysis with 73 events73 eventsndashndash 5 deaths in 5 deaths in sunitinibsunitinib

arm arm vsvs 15 in placebo 15 in placebo armarm

bullbull Study halted early Study halted early and patients on and patients on placebo given the placebo given the opportunity to cross opportunity to cross over to over to sunitinibsunitinib

Pancreatic NET

0

2

4

6

8

10

12

Medianprogressionfree survival

(months)

PlaceboSunitinib

HR 0397 2p lt0001

AccetableAccetable standard standard systemicsystemic treatmenttreatment options 2009options 2009

bullbull GEM GEM alonealonebullbull GEMGEM--erlotiniberlotinib

ndashndash registredregistred for for metastaticmetastatic PC PC onlyonly mOSmOS + 12 + 12 daysdays somesome additionaladditional toxicitytoxicity

bullbull GEMGEM--CAP CAP mOSmOS + 1 + 1 monthmonth onlyonly significantsignificant in in metameta--analysisanalysis

bullbull GEMGEM--platinumplatinum ndashndash doubtfuldoubtful effecteffect -- nownow not not significantsignificant in in metameta--

analysisanalysis significantsignificant toxicitytoxicity

ADVANCED DISEASE

SUPPORTIVE CARESUPPORTIVE CARE

Forebyggelse af venForebyggelse af venoslashoslashse se tromboembolisketromboemboliske events (VTE) ved events (VTE) ved pancreascancerpancreascancer

SUPPORTIVE CARE

GONKO 004 GONKO 004 trialtrialA prospective randomized trial of chemotherapy with or without the low molecular weight heparin (LMWH)

enoxaparin in patients (pts) with advanced pancreatic cancer (APC) Results of the CONKO 004 trial HReiss et al ASCO 2009

Baggrund

VTE forekommer hos ca 10 af patienter med PC

Formaringl

Undersoslashge effekt af LMWH (Klexane) i kombination med

kemoterapi mht frekvens af VTE og mOS

Inklusion

Avanceret PC ikke tidligere kemoterapi

Karnofsky

PS gt 60

Ingen stoslashrre bloslashdning indenfor 2 uger ingen VTE indenfor

2 aringr

SUPPORTIVE CARE

A prospective randomized trial of chemotherapy with or without the low molecular weight heparin (LMWH) enoxaparin in patients (pts) with advanced pancreatic cancer (APC) Results of the CONKO 004 trial HReiss et

al ASCO 2009

Antal af VTE 15152 i observation ndash 2160 i LMWH

SUPPORTIVE CARE

A prospective randomized trial of chemotherapy with or without the low molecular weight heparin (LMWH) enoxaparin in patients (pts) with advanced pancreatic cancer (APC) Results of the CONKO 004 trial HReiss et

al

Konklusion

LMWH er effektiv og sikker behandling til forebyggelse af

VTE hos patienter med pancreascancer

Endelige resultater paring

mOS og mTTP

afventes

SUPPORTIVE CARE

TreatmentTreatment of of malignantmalignant ascitesascites

SUPPORTIVE CARE

HeissHeiss M et al M et al CatumaxomabCatumaxomab ndashndash a new treatment option for patients a new treatment option for patients with malignant with malignant ascitesascites Ann Oncol20Suppl 7 2009 Ann Oncol20Suppl 7 2009

bullbull CatumaxomabCatumaxomab TrifunctionalTrifunctional antibody 4 antibody 4 infusions infusions ipip over 6 h in ascending doses over 6 h in ascending doses

bullbull Multicenter randomized openMulticenter randomized open--label phase label phase IIIII studyIIIII study

bullbull 258 pts with symptomatic malignant 258 pts with symptomatic malignant ascitesascites due to epithelial cancerdue to epithelial cancer

SUPPORTIVE CARE

HeissHeiss M et al M et al CatumaxomabCatumaxomab ndashndash a new treatment option for patients a new treatment option for patients with malignant with malignant ascitesascites Ann Oncol20Suppl 7 2009 Ann Oncol20Suppl 7 2009

bullbull Subgroup analysis of 129 Subgroup analysis of 129 ovarian and 129 nonovarian and 129 non-- ovarian (gastric pancreatic ovarian (gastric pancreatic CRC etc) cancer patients CRC etc) cancer patients randomizedrandomized

bullbull AEsAEs Cytokine release Cytokine release related symptoms in 80 related symptoms in 80 mostly shortmostly short--lasting and of lasting and of grade 1grade 1--22

SUPPORTIVE CARE

0

10

20

30

40

50

60

Non-ovariancancer

Ovariancancer

CatumaxomabPlacebo

Median puncture-free survival (days)

2p lt 00001

Pancreatic islet cell Pancreatic islet cell tumourstumours

Pancreatic NET

Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009

bullbull SunitinibSunitinib Oral Oral multitargetedmultitargeted tyrosine tyrosine kinasekinase inhibitor used for inhibitor used for mRCCmRCC and GISTand GIST

bullbull Phase IIPhase II--study of study of sunitinibsunitinib in NETin NET11 ORR ORR of 167 in 66 pts with of 167 in 66 pts with pNETpNET

1) Kulke MH et al JCO 263403-10 2008

Pancreatic NET

Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009

bullbull Local locally advanced or metastatic Local locally advanced or metastatic wellwell--differentiated differentiated pNETpNET not amenable to not amenable to curative therapy and with disease curative therapy and with disease progression in the prior 12 monthsprogression in the prior 12 months

bullbull Primary end point PFSPrimary end point PFSbullbull SunitinibSunitinib 375 mgday or placebo375 mgday or placebo

Pancreatic NET

Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009

bullbull 154 pts randomized154 pts randomizedbullbull Toxicity events Toxicity events sunitinibsunitinib

ndashndash Diarrhea nausea vomiting asthenia fatigueDiarrhea nausea vomiting asthenia fatiguendashndash Grade 3Grade 3--4 4 neutropenianeutropenia (12) hypertension (12) hypertension

(9) diarrhea (7) hypoglycemia (7) (9) diarrhea (7) hypoglycemia (7) palmarpalmar--plantar plantar erythrodysesthesiaerythrodysesthesia (7)(7)

Pancreatic NET

Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009

bullbull Interim analysis with Interim analysis with 73 events73 eventsndashndash 5 deaths in 5 deaths in sunitinibsunitinib

arm arm vsvs 15 in placebo 15 in placebo armarm

bullbull Study halted early Study halted early and patients on and patients on placebo given the placebo given the opportunity to cross opportunity to cross over to over to sunitinibsunitinib

Pancreatic NET

0

2

4

6

8

10

12

Medianprogressionfree survival

(months)

PlaceboSunitinib

HR 0397 2p lt0001

SUPPORTIVE CARESUPPORTIVE CARE

Forebyggelse af venForebyggelse af venoslashoslashse se tromboembolisketromboemboliske events (VTE) ved events (VTE) ved pancreascancerpancreascancer

SUPPORTIVE CARE

GONKO 004 GONKO 004 trialtrialA prospective randomized trial of chemotherapy with or without the low molecular weight heparin (LMWH)

enoxaparin in patients (pts) with advanced pancreatic cancer (APC) Results of the CONKO 004 trial HReiss et al ASCO 2009

Baggrund

VTE forekommer hos ca 10 af patienter med PC

Formaringl

Undersoslashge effekt af LMWH (Klexane) i kombination med

kemoterapi mht frekvens af VTE og mOS

Inklusion

Avanceret PC ikke tidligere kemoterapi

Karnofsky

PS gt 60

Ingen stoslashrre bloslashdning indenfor 2 uger ingen VTE indenfor

2 aringr

SUPPORTIVE CARE

A prospective randomized trial of chemotherapy with or without the low molecular weight heparin (LMWH) enoxaparin in patients (pts) with advanced pancreatic cancer (APC) Results of the CONKO 004 trial HReiss et

al ASCO 2009

Antal af VTE 15152 i observation ndash 2160 i LMWH

SUPPORTIVE CARE

A prospective randomized trial of chemotherapy with or without the low molecular weight heparin (LMWH) enoxaparin in patients (pts) with advanced pancreatic cancer (APC) Results of the CONKO 004 trial HReiss et

al

Konklusion

LMWH er effektiv og sikker behandling til forebyggelse af

VTE hos patienter med pancreascancer

Endelige resultater paring

mOS og mTTP

afventes

SUPPORTIVE CARE

TreatmentTreatment of of malignantmalignant ascitesascites

SUPPORTIVE CARE

HeissHeiss M et al M et al CatumaxomabCatumaxomab ndashndash a new treatment option for patients a new treatment option for patients with malignant with malignant ascitesascites Ann Oncol20Suppl 7 2009 Ann Oncol20Suppl 7 2009

bullbull CatumaxomabCatumaxomab TrifunctionalTrifunctional antibody 4 antibody 4 infusions infusions ipip over 6 h in ascending doses over 6 h in ascending doses

bullbull Multicenter randomized openMulticenter randomized open--label phase label phase IIIII studyIIIII study

bullbull 258 pts with symptomatic malignant 258 pts with symptomatic malignant ascitesascites due to epithelial cancerdue to epithelial cancer

SUPPORTIVE CARE

HeissHeiss M et al M et al CatumaxomabCatumaxomab ndashndash a new treatment option for patients a new treatment option for patients with malignant with malignant ascitesascites Ann Oncol20Suppl 7 2009 Ann Oncol20Suppl 7 2009

bullbull Subgroup analysis of 129 Subgroup analysis of 129 ovarian and 129 nonovarian and 129 non-- ovarian (gastric pancreatic ovarian (gastric pancreatic CRC etc) cancer patients CRC etc) cancer patients randomizedrandomized

bullbull AEsAEs Cytokine release Cytokine release related symptoms in 80 related symptoms in 80 mostly shortmostly short--lasting and of lasting and of grade 1grade 1--22

SUPPORTIVE CARE

0

10

20

30

40

50

60

Non-ovariancancer

Ovariancancer

CatumaxomabPlacebo

Median puncture-free survival (days)

2p lt 00001

Pancreatic islet cell Pancreatic islet cell tumourstumours

Pancreatic NET

Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009

bullbull SunitinibSunitinib Oral Oral multitargetedmultitargeted tyrosine tyrosine kinasekinase inhibitor used for inhibitor used for mRCCmRCC and GISTand GIST

bullbull Phase IIPhase II--study of study of sunitinibsunitinib in NETin NET11 ORR ORR of 167 in 66 pts with of 167 in 66 pts with pNETpNET

1) Kulke MH et al JCO 263403-10 2008

Pancreatic NET

Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009

bullbull Local locally advanced or metastatic Local locally advanced or metastatic wellwell--differentiated differentiated pNETpNET not amenable to not amenable to curative therapy and with disease curative therapy and with disease progression in the prior 12 monthsprogression in the prior 12 months

bullbull Primary end point PFSPrimary end point PFSbullbull SunitinibSunitinib 375 mgday or placebo375 mgday or placebo

Pancreatic NET

Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009

bullbull 154 pts randomized154 pts randomizedbullbull Toxicity events Toxicity events sunitinibsunitinib

ndashndash Diarrhea nausea vomiting asthenia fatigueDiarrhea nausea vomiting asthenia fatiguendashndash Grade 3Grade 3--4 4 neutropenianeutropenia (12) hypertension (12) hypertension

(9) diarrhea (7) hypoglycemia (7) (9) diarrhea (7) hypoglycemia (7) palmarpalmar--plantar plantar erythrodysesthesiaerythrodysesthesia (7)(7)

Pancreatic NET

Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009

bullbull Interim analysis with Interim analysis with 73 events73 eventsndashndash 5 deaths in 5 deaths in sunitinibsunitinib

arm arm vsvs 15 in placebo 15 in placebo armarm

bullbull Study halted early Study halted early and patients on and patients on placebo given the placebo given the opportunity to cross opportunity to cross over to over to sunitinibsunitinib

Pancreatic NET

0

2

4

6

8

10

12

Medianprogressionfree survival

(months)

PlaceboSunitinib

HR 0397 2p lt0001

Forebyggelse af venForebyggelse af venoslashoslashse se tromboembolisketromboemboliske events (VTE) ved events (VTE) ved pancreascancerpancreascancer

SUPPORTIVE CARE

GONKO 004 GONKO 004 trialtrialA prospective randomized trial of chemotherapy with or without the low molecular weight heparin (LMWH)

enoxaparin in patients (pts) with advanced pancreatic cancer (APC) Results of the CONKO 004 trial HReiss et al ASCO 2009

Baggrund

VTE forekommer hos ca 10 af patienter med PC

Formaringl

Undersoslashge effekt af LMWH (Klexane) i kombination med

kemoterapi mht frekvens af VTE og mOS

Inklusion

Avanceret PC ikke tidligere kemoterapi

Karnofsky

PS gt 60

Ingen stoslashrre bloslashdning indenfor 2 uger ingen VTE indenfor

2 aringr

SUPPORTIVE CARE

A prospective randomized trial of chemotherapy with or without the low molecular weight heparin (LMWH) enoxaparin in patients (pts) with advanced pancreatic cancer (APC) Results of the CONKO 004 trial HReiss et

al ASCO 2009

Antal af VTE 15152 i observation ndash 2160 i LMWH

SUPPORTIVE CARE

A prospective randomized trial of chemotherapy with or without the low molecular weight heparin (LMWH) enoxaparin in patients (pts) with advanced pancreatic cancer (APC) Results of the CONKO 004 trial HReiss et

al

Konklusion

LMWH er effektiv og sikker behandling til forebyggelse af

VTE hos patienter med pancreascancer

Endelige resultater paring

mOS og mTTP

afventes

SUPPORTIVE CARE

TreatmentTreatment of of malignantmalignant ascitesascites

SUPPORTIVE CARE

HeissHeiss M et al M et al CatumaxomabCatumaxomab ndashndash a new treatment option for patients a new treatment option for patients with malignant with malignant ascitesascites Ann Oncol20Suppl 7 2009 Ann Oncol20Suppl 7 2009

bullbull CatumaxomabCatumaxomab TrifunctionalTrifunctional antibody 4 antibody 4 infusions infusions ipip over 6 h in ascending doses over 6 h in ascending doses

bullbull Multicenter randomized openMulticenter randomized open--label phase label phase IIIII studyIIIII study

bullbull 258 pts with symptomatic malignant 258 pts with symptomatic malignant ascitesascites due to epithelial cancerdue to epithelial cancer

SUPPORTIVE CARE

HeissHeiss M et al M et al CatumaxomabCatumaxomab ndashndash a new treatment option for patients a new treatment option for patients with malignant with malignant ascitesascites Ann Oncol20Suppl 7 2009 Ann Oncol20Suppl 7 2009

bullbull Subgroup analysis of 129 Subgroup analysis of 129 ovarian and 129 nonovarian and 129 non-- ovarian (gastric pancreatic ovarian (gastric pancreatic CRC etc) cancer patients CRC etc) cancer patients randomizedrandomized

bullbull AEsAEs Cytokine release Cytokine release related symptoms in 80 related symptoms in 80 mostly shortmostly short--lasting and of lasting and of grade 1grade 1--22

SUPPORTIVE CARE

0

10

20

30

40

50

60

Non-ovariancancer

Ovariancancer

CatumaxomabPlacebo

Median puncture-free survival (days)

2p lt 00001

Pancreatic islet cell Pancreatic islet cell tumourstumours

Pancreatic NET

Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009

bullbull SunitinibSunitinib Oral Oral multitargetedmultitargeted tyrosine tyrosine kinasekinase inhibitor used for inhibitor used for mRCCmRCC and GISTand GIST

bullbull Phase IIPhase II--study of study of sunitinibsunitinib in NETin NET11 ORR ORR of 167 in 66 pts with of 167 in 66 pts with pNETpNET

1) Kulke MH et al JCO 263403-10 2008

Pancreatic NET

Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009

bullbull Local locally advanced or metastatic Local locally advanced or metastatic wellwell--differentiated differentiated pNETpNET not amenable to not amenable to curative therapy and with disease curative therapy and with disease progression in the prior 12 monthsprogression in the prior 12 months

bullbull Primary end point PFSPrimary end point PFSbullbull SunitinibSunitinib 375 mgday or placebo375 mgday or placebo

Pancreatic NET

Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009

bullbull 154 pts randomized154 pts randomizedbullbull Toxicity events Toxicity events sunitinibsunitinib

ndashndash Diarrhea nausea vomiting asthenia fatigueDiarrhea nausea vomiting asthenia fatiguendashndash Grade 3Grade 3--4 4 neutropenianeutropenia (12) hypertension (12) hypertension

(9) diarrhea (7) hypoglycemia (7) (9) diarrhea (7) hypoglycemia (7) palmarpalmar--plantar plantar erythrodysesthesiaerythrodysesthesia (7)(7)

Pancreatic NET

Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009

bullbull Interim analysis with Interim analysis with 73 events73 eventsndashndash 5 deaths in 5 deaths in sunitinibsunitinib

arm arm vsvs 15 in placebo 15 in placebo armarm

bullbull Study halted early Study halted early and patients on and patients on placebo given the placebo given the opportunity to cross opportunity to cross over to over to sunitinibsunitinib

Pancreatic NET

0

2

4

6

8

10

12

Medianprogressionfree survival

(months)

PlaceboSunitinib

HR 0397 2p lt0001

GONKO 004 GONKO 004 trialtrialA prospective randomized trial of chemotherapy with or without the low molecular weight heparin (LMWH)

enoxaparin in patients (pts) with advanced pancreatic cancer (APC) Results of the CONKO 004 trial HReiss et al ASCO 2009

Baggrund

VTE forekommer hos ca 10 af patienter med PC

Formaringl

Undersoslashge effekt af LMWH (Klexane) i kombination med

kemoterapi mht frekvens af VTE og mOS

Inklusion

Avanceret PC ikke tidligere kemoterapi

Karnofsky

PS gt 60

Ingen stoslashrre bloslashdning indenfor 2 uger ingen VTE indenfor

2 aringr

SUPPORTIVE CARE

A prospective randomized trial of chemotherapy with or without the low molecular weight heparin (LMWH) enoxaparin in patients (pts) with advanced pancreatic cancer (APC) Results of the CONKO 004 trial HReiss et

al ASCO 2009

Antal af VTE 15152 i observation ndash 2160 i LMWH

SUPPORTIVE CARE

A prospective randomized trial of chemotherapy with or without the low molecular weight heparin (LMWH) enoxaparin in patients (pts) with advanced pancreatic cancer (APC) Results of the CONKO 004 trial HReiss et

al

Konklusion

LMWH er effektiv og sikker behandling til forebyggelse af

VTE hos patienter med pancreascancer

Endelige resultater paring

mOS og mTTP

afventes

SUPPORTIVE CARE

TreatmentTreatment of of malignantmalignant ascitesascites

SUPPORTIVE CARE

HeissHeiss M et al M et al CatumaxomabCatumaxomab ndashndash a new treatment option for patients a new treatment option for patients with malignant with malignant ascitesascites Ann Oncol20Suppl 7 2009 Ann Oncol20Suppl 7 2009

bullbull CatumaxomabCatumaxomab TrifunctionalTrifunctional antibody 4 antibody 4 infusions infusions ipip over 6 h in ascending doses over 6 h in ascending doses

bullbull Multicenter randomized openMulticenter randomized open--label phase label phase IIIII studyIIIII study

bullbull 258 pts with symptomatic malignant 258 pts with symptomatic malignant ascitesascites due to epithelial cancerdue to epithelial cancer

SUPPORTIVE CARE

HeissHeiss M et al M et al CatumaxomabCatumaxomab ndashndash a new treatment option for patients a new treatment option for patients with malignant with malignant ascitesascites Ann Oncol20Suppl 7 2009 Ann Oncol20Suppl 7 2009

bullbull Subgroup analysis of 129 Subgroup analysis of 129 ovarian and 129 nonovarian and 129 non-- ovarian (gastric pancreatic ovarian (gastric pancreatic CRC etc) cancer patients CRC etc) cancer patients randomizedrandomized

bullbull AEsAEs Cytokine release Cytokine release related symptoms in 80 related symptoms in 80 mostly shortmostly short--lasting and of lasting and of grade 1grade 1--22

SUPPORTIVE CARE

0

10

20

30

40

50

60

Non-ovariancancer

Ovariancancer

CatumaxomabPlacebo

Median puncture-free survival (days)

2p lt 00001

Pancreatic islet cell Pancreatic islet cell tumourstumours

Pancreatic NET

Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009

bullbull SunitinibSunitinib Oral Oral multitargetedmultitargeted tyrosine tyrosine kinasekinase inhibitor used for inhibitor used for mRCCmRCC and GISTand GIST

bullbull Phase IIPhase II--study of study of sunitinibsunitinib in NETin NET11 ORR ORR of 167 in 66 pts with of 167 in 66 pts with pNETpNET

1) Kulke MH et al JCO 263403-10 2008

Pancreatic NET

Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009

bullbull Local locally advanced or metastatic Local locally advanced or metastatic wellwell--differentiated differentiated pNETpNET not amenable to not amenable to curative therapy and with disease curative therapy and with disease progression in the prior 12 monthsprogression in the prior 12 months

bullbull Primary end point PFSPrimary end point PFSbullbull SunitinibSunitinib 375 mgday or placebo375 mgday or placebo

Pancreatic NET

Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009

bullbull 154 pts randomized154 pts randomizedbullbull Toxicity events Toxicity events sunitinibsunitinib

ndashndash Diarrhea nausea vomiting asthenia fatigueDiarrhea nausea vomiting asthenia fatiguendashndash Grade 3Grade 3--4 4 neutropenianeutropenia (12) hypertension (12) hypertension

(9) diarrhea (7) hypoglycemia (7) (9) diarrhea (7) hypoglycemia (7) palmarpalmar--plantar plantar erythrodysesthesiaerythrodysesthesia (7)(7)

Pancreatic NET

Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009

bullbull Interim analysis with Interim analysis with 73 events73 eventsndashndash 5 deaths in 5 deaths in sunitinibsunitinib

arm arm vsvs 15 in placebo 15 in placebo armarm

bullbull Study halted early Study halted early and patients on and patients on placebo given the placebo given the opportunity to cross opportunity to cross over to over to sunitinibsunitinib

Pancreatic NET

0

2

4

6

8

10

12

Medianprogressionfree survival

(months)

PlaceboSunitinib

HR 0397 2p lt0001

A prospective randomized trial of chemotherapy with or without the low molecular weight heparin (LMWH) enoxaparin in patients (pts) with advanced pancreatic cancer (APC) Results of the CONKO 004 trial HReiss et

al ASCO 2009

Antal af VTE 15152 i observation ndash 2160 i LMWH

SUPPORTIVE CARE

A prospective randomized trial of chemotherapy with or without the low molecular weight heparin (LMWH) enoxaparin in patients (pts) with advanced pancreatic cancer (APC) Results of the CONKO 004 trial HReiss et

al

Konklusion

LMWH er effektiv og sikker behandling til forebyggelse af

VTE hos patienter med pancreascancer

Endelige resultater paring

mOS og mTTP

afventes

SUPPORTIVE CARE

TreatmentTreatment of of malignantmalignant ascitesascites

SUPPORTIVE CARE

HeissHeiss M et al M et al CatumaxomabCatumaxomab ndashndash a new treatment option for patients a new treatment option for patients with malignant with malignant ascitesascites Ann Oncol20Suppl 7 2009 Ann Oncol20Suppl 7 2009

bullbull CatumaxomabCatumaxomab TrifunctionalTrifunctional antibody 4 antibody 4 infusions infusions ipip over 6 h in ascending doses over 6 h in ascending doses

bullbull Multicenter randomized openMulticenter randomized open--label phase label phase IIIII studyIIIII study

bullbull 258 pts with symptomatic malignant 258 pts with symptomatic malignant ascitesascites due to epithelial cancerdue to epithelial cancer

SUPPORTIVE CARE

HeissHeiss M et al M et al CatumaxomabCatumaxomab ndashndash a new treatment option for patients a new treatment option for patients with malignant with malignant ascitesascites Ann Oncol20Suppl 7 2009 Ann Oncol20Suppl 7 2009

bullbull Subgroup analysis of 129 Subgroup analysis of 129 ovarian and 129 nonovarian and 129 non-- ovarian (gastric pancreatic ovarian (gastric pancreatic CRC etc) cancer patients CRC etc) cancer patients randomizedrandomized

bullbull AEsAEs Cytokine release Cytokine release related symptoms in 80 related symptoms in 80 mostly shortmostly short--lasting and of lasting and of grade 1grade 1--22

SUPPORTIVE CARE

0

10

20

30

40

50

60

Non-ovariancancer

Ovariancancer

CatumaxomabPlacebo

Median puncture-free survival (days)

2p lt 00001

Pancreatic islet cell Pancreatic islet cell tumourstumours

Pancreatic NET

Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009

bullbull SunitinibSunitinib Oral Oral multitargetedmultitargeted tyrosine tyrosine kinasekinase inhibitor used for inhibitor used for mRCCmRCC and GISTand GIST

bullbull Phase IIPhase II--study of study of sunitinibsunitinib in NETin NET11 ORR ORR of 167 in 66 pts with of 167 in 66 pts with pNETpNET

1) Kulke MH et al JCO 263403-10 2008

Pancreatic NET

Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009

bullbull Local locally advanced or metastatic Local locally advanced or metastatic wellwell--differentiated differentiated pNETpNET not amenable to not amenable to curative therapy and with disease curative therapy and with disease progression in the prior 12 monthsprogression in the prior 12 months

bullbull Primary end point PFSPrimary end point PFSbullbull SunitinibSunitinib 375 mgday or placebo375 mgday or placebo

Pancreatic NET

Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009

bullbull 154 pts randomized154 pts randomizedbullbull Toxicity events Toxicity events sunitinibsunitinib

ndashndash Diarrhea nausea vomiting asthenia fatigueDiarrhea nausea vomiting asthenia fatiguendashndash Grade 3Grade 3--4 4 neutropenianeutropenia (12) hypertension (12) hypertension

(9) diarrhea (7) hypoglycemia (7) (9) diarrhea (7) hypoglycemia (7) palmarpalmar--plantar plantar erythrodysesthesiaerythrodysesthesia (7)(7)

Pancreatic NET

Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009

bullbull Interim analysis with Interim analysis with 73 events73 eventsndashndash 5 deaths in 5 deaths in sunitinibsunitinib

arm arm vsvs 15 in placebo 15 in placebo armarm

bullbull Study halted early Study halted early and patients on and patients on placebo given the placebo given the opportunity to cross opportunity to cross over to over to sunitinibsunitinib

Pancreatic NET

0

2

4

6

8

10

12

Medianprogressionfree survival

(months)

PlaceboSunitinib

HR 0397 2p lt0001

A prospective randomized trial of chemotherapy with or without the low molecular weight heparin (LMWH) enoxaparin in patients (pts) with advanced pancreatic cancer (APC) Results of the CONKO 004 trial HReiss et

al

Konklusion

LMWH er effektiv og sikker behandling til forebyggelse af

VTE hos patienter med pancreascancer

Endelige resultater paring

mOS og mTTP

afventes

SUPPORTIVE CARE

TreatmentTreatment of of malignantmalignant ascitesascites

SUPPORTIVE CARE

HeissHeiss M et al M et al CatumaxomabCatumaxomab ndashndash a new treatment option for patients a new treatment option for patients with malignant with malignant ascitesascites Ann Oncol20Suppl 7 2009 Ann Oncol20Suppl 7 2009

bullbull CatumaxomabCatumaxomab TrifunctionalTrifunctional antibody 4 antibody 4 infusions infusions ipip over 6 h in ascending doses over 6 h in ascending doses

bullbull Multicenter randomized openMulticenter randomized open--label phase label phase IIIII studyIIIII study

bullbull 258 pts with symptomatic malignant 258 pts with symptomatic malignant ascitesascites due to epithelial cancerdue to epithelial cancer

SUPPORTIVE CARE

HeissHeiss M et al M et al CatumaxomabCatumaxomab ndashndash a new treatment option for patients a new treatment option for patients with malignant with malignant ascitesascites Ann Oncol20Suppl 7 2009 Ann Oncol20Suppl 7 2009

bullbull Subgroup analysis of 129 Subgroup analysis of 129 ovarian and 129 nonovarian and 129 non-- ovarian (gastric pancreatic ovarian (gastric pancreatic CRC etc) cancer patients CRC etc) cancer patients randomizedrandomized

bullbull AEsAEs Cytokine release Cytokine release related symptoms in 80 related symptoms in 80 mostly shortmostly short--lasting and of lasting and of grade 1grade 1--22

SUPPORTIVE CARE

0

10

20

30

40

50

60

Non-ovariancancer

Ovariancancer

CatumaxomabPlacebo

Median puncture-free survival (days)

2p lt 00001

Pancreatic islet cell Pancreatic islet cell tumourstumours

Pancreatic NET

Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009

bullbull SunitinibSunitinib Oral Oral multitargetedmultitargeted tyrosine tyrosine kinasekinase inhibitor used for inhibitor used for mRCCmRCC and GISTand GIST

bullbull Phase IIPhase II--study of study of sunitinibsunitinib in NETin NET11 ORR ORR of 167 in 66 pts with of 167 in 66 pts with pNETpNET

1) Kulke MH et al JCO 263403-10 2008

Pancreatic NET

Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009

bullbull Local locally advanced or metastatic Local locally advanced or metastatic wellwell--differentiated differentiated pNETpNET not amenable to not amenable to curative therapy and with disease curative therapy and with disease progression in the prior 12 monthsprogression in the prior 12 months

bullbull Primary end point PFSPrimary end point PFSbullbull SunitinibSunitinib 375 mgday or placebo375 mgday or placebo

Pancreatic NET

Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009

bullbull 154 pts randomized154 pts randomizedbullbull Toxicity events Toxicity events sunitinibsunitinib

ndashndash Diarrhea nausea vomiting asthenia fatigueDiarrhea nausea vomiting asthenia fatiguendashndash Grade 3Grade 3--4 4 neutropenianeutropenia (12) hypertension (12) hypertension

(9) diarrhea (7) hypoglycemia (7) (9) diarrhea (7) hypoglycemia (7) palmarpalmar--plantar plantar erythrodysesthesiaerythrodysesthesia (7)(7)

Pancreatic NET

Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009

bullbull Interim analysis with Interim analysis with 73 events73 eventsndashndash 5 deaths in 5 deaths in sunitinibsunitinib

arm arm vsvs 15 in placebo 15 in placebo armarm

bullbull Study halted early Study halted early and patients on and patients on placebo given the placebo given the opportunity to cross opportunity to cross over to over to sunitinibsunitinib

Pancreatic NET

0

2

4

6

8

10

12

Medianprogressionfree survival

(months)

PlaceboSunitinib

HR 0397 2p lt0001

TreatmentTreatment of of malignantmalignant ascitesascites

SUPPORTIVE CARE

HeissHeiss M et al M et al CatumaxomabCatumaxomab ndashndash a new treatment option for patients a new treatment option for patients with malignant with malignant ascitesascites Ann Oncol20Suppl 7 2009 Ann Oncol20Suppl 7 2009

bullbull CatumaxomabCatumaxomab TrifunctionalTrifunctional antibody 4 antibody 4 infusions infusions ipip over 6 h in ascending doses over 6 h in ascending doses

bullbull Multicenter randomized openMulticenter randomized open--label phase label phase IIIII studyIIIII study

bullbull 258 pts with symptomatic malignant 258 pts with symptomatic malignant ascitesascites due to epithelial cancerdue to epithelial cancer

SUPPORTIVE CARE

HeissHeiss M et al M et al CatumaxomabCatumaxomab ndashndash a new treatment option for patients a new treatment option for patients with malignant with malignant ascitesascites Ann Oncol20Suppl 7 2009 Ann Oncol20Suppl 7 2009

bullbull Subgroup analysis of 129 Subgroup analysis of 129 ovarian and 129 nonovarian and 129 non-- ovarian (gastric pancreatic ovarian (gastric pancreatic CRC etc) cancer patients CRC etc) cancer patients randomizedrandomized

bullbull AEsAEs Cytokine release Cytokine release related symptoms in 80 related symptoms in 80 mostly shortmostly short--lasting and of lasting and of grade 1grade 1--22

SUPPORTIVE CARE

0

10

20

30

40

50

60

Non-ovariancancer

Ovariancancer

CatumaxomabPlacebo

Median puncture-free survival (days)

2p lt 00001

Pancreatic islet cell Pancreatic islet cell tumourstumours

Pancreatic NET

Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009

bullbull SunitinibSunitinib Oral Oral multitargetedmultitargeted tyrosine tyrosine kinasekinase inhibitor used for inhibitor used for mRCCmRCC and GISTand GIST

bullbull Phase IIPhase II--study of study of sunitinibsunitinib in NETin NET11 ORR ORR of 167 in 66 pts with of 167 in 66 pts with pNETpNET

1) Kulke MH et al JCO 263403-10 2008

Pancreatic NET

Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009

bullbull Local locally advanced or metastatic Local locally advanced or metastatic wellwell--differentiated differentiated pNETpNET not amenable to not amenable to curative therapy and with disease curative therapy and with disease progression in the prior 12 monthsprogression in the prior 12 months

bullbull Primary end point PFSPrimary end point PFSbullbull SunitinibSunitinib 375 mgday or placebo375 mgday or placebo

Pancreatic NET

Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009

bullbull 154 pts randomized154 pts randomizedbullbull Toxicity events Toxicity events sunitinibsunitinib

ndashndash Diarrhea nausea vomiting asthenia fatigueDiarrhea nausea vomiting asthenia fatiguendashndash Grade 3Grade 3--4 4 neutropenianeutropenia (12) hypertension (12) hypertension

(9) diarrhea (7) hypoglycemia (7) (9) diarrhea (7) hypoglycemia (7) palmarpalmar--plantar plantar erythrodysesthesiaerythrodysesthesia (7)(7)

Pancreatic NET

Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009

bullbull Interim analysis with Interim analysis with 73 events73 eventsndashndash 5 deaths in 5 deaths in sunitinibsunitinib

arm arm vsvs 15 in placebo 15 in placebo armarm

bullbull Study halted early Study halted early and patients on and patients on placebo given the placebo given the opportunity to cross opportunity to cross over to over to sunitinibsunitinib

Pancreatic NET

0

2

4

6

8

10

12

Medianprogressionfree survival

(months)

PlaceboSunitinib

HR 0397 2p lt0001

HeissHeiss M et al M et al CatumaxomabCatumaxomab ndashndash a new treatment option for patients a new treatment option for patients with malignant with malignant ascitesascites Ann Oncol20Suppl 7 2009 Ann Oncol20Suppl 7 2009

bullbull CatumaxomabCatumaxomab TrifunctionalTrifunctional antibody 4 antibody 4 infusions infusions ipip over 6 h in ascending doses over 6 h in ascending doses

bullbull Multicenter randomized openMulticenter randomized open--label phase label phase IIIII studyIIIII study

bullbull 258 pts with symptomatic malignant 258 pts with symptomatic malignant ascitesascites due to epithelial cancerdue to epithelial cancer

SUPPORTIVE CARE

HeissHeiss M et al M et al CatumaxomabCatumaxomab ndashndash a new treatment option for patients a new treatment option for patients with malignant with malignant ascitesascites Ann Oncol20Suppl 7 2009 Ann Oncol20Suppl 7 2009

bullbull Subgroup analysis of 129 Subgroup analysis of 129 ovarian and 129 nonovarian and 129 non-- ovarian (gastric pancreatic ovarian (gastric pancreatic CRC etc) cancer patients CRC etc) cancer patients randomizedrandomized

bullbull AEsAEs Cytokine release Cytokine release related symptoms in 80 related symptoms in 80 mostly shortmostly short--lasting and of lasting and of grade 1grade 1--22

SUPPORTIVE CARE

0

10

20

30

40

50

60

Non-ovariancancer

Ovariancancer

CatumaxomabPlacebo

Median puncture-free survival (days)

2p lt 00001

Pancreatic islet cell Pancreatic islet cell tumourstumours

Pancreatic NET

Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009

bullbull SunitinibSunitinib Oral Oral multitargetedmultitargeted tyrosine tyrosine kinasekinase inhibitor used for inhibitor used for mRCCmRCC and GISTand GIST

bullbull Phase IIPhase II--study of study of sunitinibsunitinib in NETin NET11 ORR ORR of 167 in 66 pts with of 167 in 66 pts with pNETpNET

1) Kulke MH et al JCO 263403-10 2008

Pancreatic NET

Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009

bullbull Local locally advanced or metastatic Local locally advanced or metastatic wellwell--differentiated differentiated pNETpNET not amenable to not amenable to curative therapy and with disease curative therapy and with disease progression in the prior 12 monthsprogression in the prior 12 months

bullbull Primary end point PFSPrimary end point PFSbullbull SunitinibSunitinib 375 mgday or placebo375 mgday or placebo

Pancreatic NET

Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009

bullbull 154 pts randomized154 pts randomizedbullbull Toxicity events Toxicity events sunitinibsunitinib

ndashndash Diarrhea nausea vomiting asthenia fatigueDiarrhea nausea vomiting asthenia fatiguendashndash Grade 3Grade 3--4 4 neutropenianeutropenia (12) hypertension (12) hypertension

(9) diarrhea (7) hypoglycemia (7) (9) diarrhea (7) hypoglycemia (7) palmarpalmar--plantar plantar erythrodysesthesiaerythrodysesthesia (7)(7)

Pancreatic NET

Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009

bullbull Interim analysis with Interim analysis with 73 events73 eventsndashndash 5 deaths in 5 deaths in sunitinibsunitinib

arm arm vsvs 15 in placebo 15 in placebo armarm

bullbull Study halted early Study halted early and patients on and patients on placebo given the placebo given the opportunity to cross opportunity to cross over to over to sunitinibsunitinib

Pancreatic NET

0

2

4

6

8

10

12

Medianprogressionfree survival

(months)

PlaceboSunitinib

HR 0397 2p lt0001

HeissHeiss M et al M et al CatumaxomabCatumaxomab ndashndash a new treatment option for patients a new treatment option for patients with malignant with malignant ascitesascites Ann Oncol20Suppl 7 2009 Ann Oncol20Suppl 7 2009

bullbull Subgroup analysis of 129 Subgroup analysis of 129 ovarian and 129 nonovarian and 129 non-- ovarian (gastric pancreatic ovarian (gastric pancreatic CRC etc) cancer patients CRC etc) cancer patients randomizedrandomized

bullbull AEsAEs Cytokine release Cytokine release related symptoms in 80 related symptoms in 80 mostly shortmostly short--lasting and of lasting and of grade 1grade 1--22

SUPPORTIVE CARE

0

10

20

30

40

50

60

Non-ovariancancer

Ovariancancer

CatumaxomabPlacebo

Median puncture-free survival (days)

2p lt 00001

Pancreatic islet cell Pancreatic islet cell tumourstumours

Pancreatic NET

Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009

bullbull SunitinibSunitinib Oral Oral multitargetedmultitargeted tyrosine tyrosine kinasekinase inhibitor used for inhibitor used for mRCCmRCC and GISTand GIST

bullbull Phase IIPhase II--study of study of sunitinibsunitinib in NETin NET11 ORR ORR of 167 in 66 pts with of 167 in 66 pts with pNETpNET

1) Kulke MH et al JCO 263403-10 2008

Pancreatic NET

Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009

bullbull Local locally advanced or metastatic Local locally advanced or metastatic wellwell--differentiated differentiated pNETpNET not amenable to not amenable to curative therapy and with disease curative therapy and with disease progression in the prior 12 monthsprogression in the prior 12 months

bullbull Primary end point PFSPrimary end point PFSbullbull SunitinibSunitinib 375 mgday or placebo375 mgday or placebo

Pancreatic NET

Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009

bullbull 154 pts randomized154 pts randomizedbullbull Toxicity events Toxicity events sunitinibsunitinib

ndashndash Diarrhea nausea vomiting asthenia fatigueDiarrhea nausea vomiting asthenia fatiguendashndash Grade 3Grade 3--4 4 neutropenianeutropenia (12) hypertension (12) hypertension

(9) diarrhea (7) hypoglycemia (7) (9) diarrhea (7) hypoglycemia (7) palmarpalmar--plantar plantar erythrodysesthesiaerythrodysesthesia (7)(7)

Pancreatic NET

Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009

bullbull Interim analysis with Interim analysis with 73 events73 eventsndashndash 5 deaths in 5 deaths in sunitinibsunitinib

arm arm vsvs 15 in placebo 15 in placebo armarm

bullbull Study halted early Study halted early and patients on and patients on placebo given the placebo given the opportunity to cross opportunity to cross over to over to sunitinibsunitinib

Pancreatic NET

0

2

4

6

8

10

12

Medianprogressionfree survival

(months)

PlaceboSunitinib

HR 0397 2p lt0001

Pancreatic islet cell Pancreatic islet cell tumourstumours

Pancreatic NET

Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009

bullbull SunitinibSunitinib Oral Oral multitargetedmultitargeted tyrosine tyrosine kinasekinase inhibitor used for inhibitor used for mRCCmRCC and GISTand GIST

bullbull Phase IIPhase II--study of study of sunitinibsunitinib in NETin NET11 ORR ORR of 167 in 66 pts with of 167 in 66 pts with pNETpNET

1) Kulke MH et al JCO 263403-10 2008

Pancreatic NET

Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009

bullbull Local locally advanced or metastatic Local locally advanced or metastatic wellwell--differentiated differentiated pNETpNET not amenable to not amenable to curative therapy and with disease curative therapy and with disease progression in the prior 12 monthsprogression in the prior 12 months

bullbull Primary end point PFSPrimary end point PFSbullbull SunitinibSunitinib 375 mgday or placebo375 mgday or placebo

Pancreatic NET

Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009

bullbull 154 pts randomized154 pts randomizedbullbull Toxicity events Toxicity events sunitinibsunitinib

ndashndash Diarrhea nausea vomiting asthenia fatigueDiarrhea nausea vomiting asthenia fatiguendashndash Grade 3Grade 3--4 4 neutropenianeutropenia (12) hypertension (12) hypertension

(9) diarrhea (7) hypoglycemia (7) (9) diarrhea (7) hypoglycemia (7) palmarpalmar--plantar plantar erythrodysesthesiaerythrodysesthesia (7)(7)

Pancreatic NET

Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009

bullbull Interim analysis with Interim analysis with 73 events73 eventsndashndash 5 deaths in 5 deaths in sunitinibsunitinib

arm arm vsvs 15 in placebo 15 in placebo armarm

bullbull Study halted early Study halted early and patients on and patients on placebo given the placebo given the opportunity to cross opportunity to cross over to over to sunitinibsunitinib

Pancreatic NET

0

2

4

6

8

10

12

Medianprogressionfree survival

(months)

PlaceboSunitinib

HR 0397 2p lt0001

Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009

bullbull SunitinibSunitinib Oral Oral multitargetedmultitargeted tyrosine tyrosine kinasekinase inhibitor used for inhibitor used for mRCCmRCC and GISTand GIST

bullbull Phase IIPhase II--study of study of sunitinibsunitinib in NETin NET11 ORR ORR of 167 in 66 pts with of 167 in 66 pts with pNETpNET

1) Kulke MH et al JCO 263403-10 2008

Pancreatic NET

Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009

bullbull Local locally advanced or metastatic Local locally advanced or metastatic wellwell--differentiated differentiated pNETpNET not amenable to not amenable to curative therapy and with disease curative therapy and with disease progression in the prior 12 monthsprogression in the prior 12 months

bullbull Primary end point PFSPrimary end point PFSbullbull SunitinibSunitinib 375 mgday or placebo375 mgday or placebo

Pancreatic NET

Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009

bullbull 154 pts randomized154 pts randomizedbullbull Toxicity events Toxicity events sunitinibsunitinib

ndashndash Diarrhea nausea vomiting asthenia fatigueDiarrhea nausea vomiting asthenia fatiguendashndash Grade 3Grade 3--4 4 neutropenianeutropenia (12) hypertension (12) hypertension

(9) diarrhea (7) hypoglycemia (7) (9) diarrhea (7) hypoglycemia (7) palmarpalmar--plantar plantar erythrodysesthesiaerythrodysesthesia (7)(7)

Pancreatic NET

Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009

bullbull Interim analysis with Interim analysis with 73 events73 eventsndashndash 5 deaths in 5 deaths in sunitinibsunitinib

arm arm vsvs 15 in placebo 15 in placebo armarm

bullbull Study halted early Study halted early and patients on and patients on placebo given the placebo given the opportunity to cross opportunity to cross over to over to sunitinibsunitinib

Pancreatic NET

0

2

4

6

8

10

12

Medianprogressionfree survival

(months)

PlaceboSunitinib

HR 0397 2p lt0001

Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009

bullbull Local locally advanced or metastatic Local locally advanced or metastatic wellwell--differentiated differentiated pNETpNET not amenable to not amenable to curative therapy and with disease curative therapy and with disease progression in the prior 12 monthsprogression in the prior 12 months

bullbull Primary end point PFSPrimary end point PFSbullbull SunitinibSunitinib 375 mgday or placebo375 mgday or placebo

Pancreatic NET

Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009

bullbull 154 pts randomized154 pts randomizedbullbull Toxicity events Toxicity events sunitinibsunitinib

ndashndash Diarrhea nausea vomiting asthenia fatigueDiarrhea nausea vomiting asthenia fatiguendashndash Grade 3Grade 3--4 4 neutropenianeutropenia (12) hypertension (12) hypertension

(9) diarrhea (7) hypoglycemia (7) (9) diarrhea (7) hypoglycemia (7) palmarpalmar--plantar plantar erythrodysesthesiaerythrodysesthesia (7)(7)

Pancreatic NET

Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009

bullbull Interim analysis with Interim analysis with 73 events73 eventsndashndash 5 deaths in 5 deaths in sunitinibsunitinib

arm arm vsvs 15 in placebo 15 in placebo armarm

bullbull Study halted early Study halted early and patients on and patients on placebo given the placebo given the opportunity to cross opportunity to cross over to over to sunitinibsunitinib

Pancreatic NET

0

2

4

6

8

10

12

Medianprogressionfree survival

(months)

PlaceboSunitinib

HR 0397 2p lt0001

Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009

bullbull 154 pts randomized154 pts randomizedbullbull Toxicity events Toxicity events sunitinibsunitinib

ndashndash Diarrhea nausea vomiting asthenia fatigueDiarrhea nausea vomiting asthenia fatiguendashndash Grade 3Grade 3--4 4 neutropenianeutropenia (12) hypertension (12) hypertension

(9) diarrhea (7) hypoglycemia (7) (9) diarrhea (7) hypoglycemia (7) palmarpalmar--plantar plantar erythrodysesthesiaerythrodysesthesia (7)(7)

Pancreatic NET

Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009

bullbull Interim analysis with Interim analysis with 73 events73 eventsndashndash 5 deaths in 5 deaths in sunitinibsunitinib

arm arm vsvs 15 in placebo 15 in placebo armarm

bullbull Study halted early Study halted early and patients on and patients on placebo given the placebo given the opportunity to cross opportunity to cross over to over to sunitinibsunitinib

Pancreatic NET

0

2

4

6

8

10

12

Medianprogressionfree survival

(months)

PlaceboSunitinib

HR 0397 2p lt0001

Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009

bullbull Interim analysis with Interim analysis with 73 events73 eventsndashndash 5 deaths in 5 deaths in sunitinibsunitinib

arm arm vsvs 15 in placebo 15 in placebo armarm

bullbull Study halted early Study halted early and patients on and patients on placebo given the placebo given the opportunity to cross opportunity to cross over to over to sunitinibsunitinib

Pancreatic NET

0

2

4

6

8

10

12

Medianprogressionfree survival

(months)

PlaceboSunitinib

HR 0397 2p lt0001