avances en el tratamiento del cáncer gástrico y esofágico€¦ · tratamiento de la enfermedad...

Avances en el tratamiento del Cáncer Gástrico y Esofágico

Fernando Rivera HerreroHospital Universitario Marqués de Valdecilla, Santander

Introducción Tratamiento de la Enfermedad Resecable

Ca. Esofago Adenoca Gástrico Adenoca de la UEG Nuevas dianas

Tratamiento de la Enfermedad Avanzada Ca. Epidermoide de esófago Adenoca del esofago distal, la UEG y gástrico

Quimioterapia Nuevas dianas


Cáncer Esófago-Gástrico Grupo heterogéneo de enfermedades

Cáncer de esófago

- Ca. Epidermoide- Adenocarcinoma

Adenocarcinoma de la UEG

Adenoca. Gástrico

Gastric Cancer: Comprehensive Molecular Characterization

Esophageal Cancer Gastric CancerPts 5y OS* Pts 5y OS*

Early disease 10% 70% 10% 70%(T1-2 N0 M0)

Locally advanced 50% 30% 40% 30%resectable (T3-4, N+, M0)

Locally advanced 25% <5% 20% <5%unresectable Metastatic 15% <5% 30% <5%

(M1)*5y OS with Surgery alone

Esophago-Gastric Cancer Resectability at Diagnosis





Avances en el tratamiento del cáncer Gástrico y Esofágico

Treatment options in Resectable -Esophageal Cancer

- EGJ Adenocarcinoma- Gastric Adenocarcinoma

- Definitive chemoradiotherapy- Preoperative Chemotherapy- Preoperative Chemo-RadiotherapyEsophageal

Cancer

Gastric Cancer

- Perioperative Chemotherapy- Postoperative Chemo-Radiotherapy- Postoperative Chemotherapy ??

- Preoperative Chemo-Radiotherapy- Perioperative Chemotherapy




Cancer

Definitive Chemo-Radiotherapy

F III RTOG 85-01: QT/RT vs RT(Herskowic, N Engl J Med, 1992)

123 pts(87% Squamous)

RT (64 Gy)

LR control (5y) 34% 53%P<0.05

PF, PF, PF,PFRT (50Gy)

Systemic control (1y) 71% 84%P<0.05

Survival (5y) 0% 28%P<0.05

If no resection, CT/RT is the gold standard

QT/RT definitiva en C. Esófago

267 PTSCa esófago (Epid/Aden)Est I-IVA

CF/RT4 ciclos, 2 concomitantes

con 50Gy de RT

FOLFOX /RT6 ciclos, 3 concomitantes

con 50Gy de RT

F. III PRODIGE 5/ACCORD 17 1

Objetivo 1º: SLP (mediana) 9,7 m HR 0,93; p 0,64 9,4 mFOLFOX/RT menos tóxico

102 PTSCa esófago (Epid/Aden)Est I-IVA

CF/RTCarbo-Pacli /RT

E. Retrospectivo holandés (no randomizado) 2

Sv (mediana) 13,8 m HR 0,97; p 0,87 16,1 mSLP (mediana) 9,7 m HR 0,93; p 0,76 11,1 m

Carbo-Pacli/RT menos tóxico

1.- Conroy T et al. Lancet Oncology 2014; 2.- Honing J et al. Ann Oncol 2014




Cancer

Preoperative ChemotherapyPhase III studies

Phase III Preop.CT N Pts Histol. Sv (3y,median) Preop CT vs Surg.

pRC

Hatlevoll Cis/Bleo 97 Squam. 3% vs 9%

Roth Cis/Vds/Bleo 39 Squam. 25% vs 5%

Schlag Cis/5-FU 75 Squam. 10m vs 10m

Kok Cis/Etop 171 Squam. 18,5m vs 15m *

INT 113 Cis/5-FU x 3 440 51%Aden. 23% vs 26% 2,5%

MRC OE-02 Cis/5-FU x 2 802 66%Aden 34% vs 26% * 3%

* P<0.05

Preoperative Chemo-RadiotherapyPhase III studies

Phase III

Preop CT-RT

N

Histol.

3y Sv CT/RT/S vs Surg

Postoper. Mortality CT/RT/S vs Surg

pRC

Nygaard Cis-Bleo 35Gy 88 Squam 21% vs 9% 13% vs 24%

Le Prise Cis-5FU 20Gy 86 Squam 19% vs 14% 8% vs 7%

Walsh Cis-5FU / 40Gy 113 Adenoc 32% vs 6% * 12% vs 4% 25%

EORTC Cis / 37Gy(3,7x10) 282 Squam 34% vs 36% 16% vs 5%* 26%

Urba Cis-5FU-Vbl/ 45Gy 100 75%Ade 30% vs 16% 2% vs 4% 28%

Lee Cis/5FU/45Gy(28d) 101 Squam 45% vs 40% 30%

Burmeister Cis-5FU / 35Gy 256 63%Ade 35% vs 31% 16%

CALGB-9781 Cis-5FU / 50Gy 56 75%Ade (5a)39% vs 16%* 0% vs 8% 40%

CROSS ASCO-10 #4004

Pacli-Carbo/ 41Gy 363 75% Ade 59% vs 48%* 3,8% vs 3,7% 33%

QT vs QT/RT Preoperatoria en Ca Esófago

Estudios / pts10 1209

SupervivenciaHR 0,81(0,7-0,93) p 0,002

Dif absoluta Sv 2a13 %

Meta-análisis Gebski et al, Lancet Oncology 07

Estudios / pts8 1724

SupervivenciaHR 0,9(0,81-1) p 0,05

Dif absoluta Sv 2a7 %

QT/RT preCx

QT preCx

Is it possible to avoid Surgeryafter CT/RT?

- In all patients?

QT/RT Surgery vs QT/RT

Phase III Stahl (Stahl, J Clin Oncol 2005)(only Squamous) 172 pts

Loco-Regional Control Survival

Is it possible to avoid Surgeryafter CT/RT?

- Only in initially responding patients?

Phase III FFCD 9102 (Bedenne et al, J Clin Oncol, 2007)

Phase III: FFCD 9102(Bedenne, J Clin Oncol, 2007)

Resectable Stage II-IV (M0)Squamous 90% 455 pts received CFx2 / 46Gy

PR: 259 pts

Sv (2y) 34% p NS 40%LRC(2y) 66,4 p NS 57%Treat.Mortality 9% 1%Q of L better

Surgery CT/RTCFx1 / 20Gy



Gastric Cancer

- Postoperative Chemotherapy -Postoperative Chemo-Radiotherapy - Perioperative Chemotherapy



Gastric Cancer

- Postoperative Chemotherapy ??-Postoperative Chemo-Radiotherapy - Perioperative Chemotherapy

GASTRIC “GLOBAL ADVANCED/ADJUVANT STOMACH TUMOR RESEARCH THROUGH INTERNATIONAL COLLABORATION”

JAMA. 201 0 MAY 5;303(1 7): 1 729- 37

Meta-Analysis 17 phase III trials 3 838 ptsIndividual data

HR: 0,82 (0,76-0,90)

5y OS: 55% vs 49%

Sakuramoto S et al, NEJM-07

1059 PTSR0 Resected Gastric adenocarc.St II-IV, D2+ nodal dissection No Postop

treatmentPostoperative S-1(S1 80mg/m2/d,

d 1-28 each 42d, 1 year)

Postoperative Chemotherapy: S-1Phase III ACTS-GC (Japan)

Primary endpoint: Sv

S1 No CT HR p Sv (3y) 80% vs 70% 0.68 0.003

Postoperative Chemotherapy

1035 PTSR0 resected Gastric cancer, D2St II-IIIB SurgerySurgery XELOX

Primary endpoint: SLP

Phase III CLASSIC (Asia)

HR p . SLP (3y) 74% 0.58 <0.001 60%

Obj 2º OSMedian follow-up 34 m

Bang et al. Lancet. 2012 (Preplanned interim analysis)



Gastric Cancer


Postoperative Chemo-RadiotherapySWOG 9008/INT 0116

Macdonald et al, N Engl J Med 2001

566 PTSR0, St.IB-IV (M0)

Gastric 80% E-G Junction 20% No Postop

treatmentCT/RTFU-Lv x5 / (45 Gy)

Sv (3 y) 50% p=0.005 41%Loc.Relap(3y) 19% p=0.005 29% Dist.Relap(3y) 33% 18%

Survival

(MacDonald JS et al. ASCO-04)

INT 0116Survival according to Histology

Intestinal (61% of pts) Diffuse (39% of pts)

Postoperative Chemo-Radiotherapy

546 PTS R0 resected Gastric C.

Surgery ECFx2F/RTECFx2

Surgery FLx2F/RTFLx2

Primary endpoint: OS

P. III CALGB 80101(US-Intergroup)

- Survival (median/3y) 37m /50% HR 1,03 p 0,8 38m/52%- DFS (median/3y) 30m /46% HR 1,03 p 0,8 28m/47%- G 4 Tox 40% p<0,001 26%

(Fuchs, ASCO 2011#4003)

Postoperative Chemo-Radiotherapy

- DFS (3y) 74% HR 0,74 p 0,09 78%intestinal 83% p 0,01 94% pN+ 72% p 0,04 76%

- LR relapse 13% p 0,03 7%- OS (3y) 87% HR 1,13 p 0,52 84%

Lee J et al. ASCO 2014- #4008

OSDFS

458 PTS R0 resected Gastric cancer, D2St II-IV

SurgeryXP/RTSurgery XP

P. III ARTIST (Korea)

1º endpoint: DFS

POSTOPERATIVE CHEMO-RADIOTHERAPYP. III ARTIST (Korea)

Lee J et al. ASCO 2014- #4008



Gastric Cancer


Perioperative Chemotherapy MAGIC-1

Cunningham et al, N Engl J Med 2006

503 PTSResectable St. II-IV (M0)Gastric 74% E-G Junction 26%

SurgeryPerioperative CTECFx3Surg.ECFx3

(44% of pts)

Sv (3y) 43% p<0.05 32%Loc Rel (3y): 29% p<0.05 44%Dist Rel (3y): 31% p<0.05 45%

Survival

Boige V et al, ASCO-07 # 4510

224 PTSResectable adenocarcinoma -Gastric (no EGJ) 25 % -EGJ 64 %-distal esophagous 11 %

PS 0 / 1 (75% / 25%)

SurgeryPerioperative CTCFx2-3Surgery(CF x4 postSx if OR or SD with pN+: 50% pts)

CFSur Sur HR p Sv (5y) 38% vs 24% 0,66 0,01DFS (5y) 34% vs 21% 0,65 0,003

Perioperative ChemotherapyPhase III FNLCC-ACCORD07-FFCD 9703

Primary endpoint: Sv

Perioperative CT vs Postoperative CT/RTMAGIC-1: 503 PTS

ECFx3CxECFx3 vs Cx

Sv

Cunningham et al, N Engl J Med 2006

FIII 9703: 224 PTSCFx2-3CxCFx4 vs Cx

Boige V et al, ASCO-07 # 4510

Sv

Sv

INT 0116: 566 PTSCx FU-LV/RT vs Cx

Macdonald et al, N Engl J Med 2001

Should RT be added to perioperative CT?

- Perioperative Chemotherapy does not include RT- The addition of RT to Perioperat CT is “investigational”

788 PTSResectable Gastric Cancer St.

II-IV (M0)Primary end point: Survival

Perioperative CTECX x3Surg. ECX x3

Preop CT + Postop CT/RTECX x3Surg. RT/Xeloda

F. III CRITICS (Dutch)

Stahl et al. J Clin Oncol 2009; 27: 851-856

119 Pts in 5 y (planned 177)Siewert I / II-III 55%/45%ECOG 0/1 60%/40%Weight loss >10% 16%

Preop CT/RT PFLx2PE/RTCx

OS (3y) 27% HR 0.67 (0.41-1.07) p 0.07 47%Local Control (3y) 59% HR 0,45 (0,19-1,05) p 0.06 76%R0 69% p NS 72%pCR 2% p 0.03 16%Perioperative Mort. 4% p 0.26 10%

Resectable EGJ adenocarcinomaF. III POET (Preop CT vs Preop CT-RT)


Preop. CTPFLx3Cx

Resectable EGJ AdenocaPhase III POET

Sv

Control Local27.7%

36%

Perioperative Chemotherapy in EGJ Adenoca

1.- Cunningham et al, N Engl J Med 20062.- Boige et al, ASCO 2007 # 4510

131 pts included with - Distal esophageal adenoca (73 pts) - EGJ adenoca (58 pts)

MAGIC 1

FNLCC 2 64% o pts (143 pts) included with - EGJ adenoca

EGJ AdenocarcinomaSiewert Clasification

«Esophageal» options? Preop CT/RT

«Gastric» options? Perioperative CT

Cetuximab-QT/RT: Ca esófago no metastásico…dos Fases III negativos

258 PTS (no se paso a F.III por análisis de futilidad)

Ca esófago (Epid/Aden)Est I-III

Cis-Cape/RT4 ciclos, 3º-4ºcon 50Gy

Cetuxi+Cis-Cape/RT4 ciclos, 3º-4º con 50Gy

F. II-III SCOPE 1 1

Objetivo 1º F II: TTF (24 sem) 66% 77% Sv (mediana) 22,1m HR 1,53; p 0,03 25,4m

Más Toxicidad en brazo con Cetuximab

1.- Crosby T el al. Lancet Oncology 2013 ; 2.- Suntharalingam et al, ASCO-GI 2014

328 PTS Ca esófago (Adenoc 62%)Est I-IVA

Cis-Paclitaxel/RT50Gy

Cetuxi+Cis-Pacli/RT50Gy

F.III RTOG 0436 2

Objetivo 1º Sv (12 m) 64% p 0,7 65% Sv (24 m) 44% p 0,7 42%

No diferencias en Ca epiderm y Adenoca

MAGIC-B, MRC-ST03 (ECX ± Bevacizumab)

– Phase III (N=950) - Primary Objetive: Overall Survival

UK MRC ST03 (MAGIC-B) Phase III trial:ECX ± Beva (perioperative) in early stage GC

Gastric or GEJ Cancertype III resectable

N=950

ECX3 cycles

ECX + Avastin3 cycles

ECX3 cycles

ECX + Avastin3 cycles

SurgeryAvastin

6 cycles

ECX (q3w)Epirubicina 50mg/m2 d1Cisplatin 60mg/m2 d1Capecitabine 1250mg/m2 d1-21

Bevacizumab 7.5mg/kg d1q3w

5w (ECX)8w (ECX-B)

6-10w

Studies with trastuzumab in resectable Her2+ esophago-gastric adenocarcinoma

36 PtsResectable Her2 +,Gastric-EGJ Cancer

Primary endpoint: DFS

Perioperative Xelox-Trastuz.Xelox-T x3Surg. Xelox-T x3Tx12

P. II NEOXH (Spain)

53 Pts Resectable Her 2+, Gastric-EGJ Cancer

Primary endpoint: pCR

Perioperative FLOT-Trastuz.FLOT-T x4Surg. FLOT-T x4Tx9

P II AIO-STO 0310 (Germany)

(Hofheinz R et al, ASCO 2014, #4073) R0: 93% , pCR: 22%

(Rivera F et al, ASCO-GI 2015 #107) R0: 78% (MAGIC: 69%)pCR: 8% (MAGIC: 0%)

24 m PFS: 60% (MAGIC: 45%)24 m OS: 75% (MAGIC: 50)

USO EXPERIMENTAL/FUERA DE INDICACIÓN

Studies with trastuzumab in resectable Her2+ esophago-gastric adenocarcinoma

160 PtsResectable Her2+ Esoph-EGJ Adenoca

Primary endpoint: DFS

Preop.CarbTax-RT CarbTax/RT 50Gy Surg. P III RTOG 1010 (USA)

Preop.CarbTax-RT+ Periop.Trastuz.T-CarbTax/RT 50Gy Surg. Tx13







Cisplatino-Fluoropirimidina…..¿Carboplatino?…..¿Taxanos?… antiEGFR MoAb en investigación

Chemotherapy

0 5 10 15

EOX (6)XP (7)

ECX (6)ECF (6)DCF (4)EOF (6)

IF (5)CF (4)

FAMTX (2)BSC (1)

Months

C+S1 (3)

1Murad et al 1993; 2Vanhoefer et al 2000; 3Ajani et al 2009;

4Van Cutsem et al 2006; 5Dank et al 2008; 6Cunningham et al 2008; 7Kang et al 2009;

8Van Cutsem et al 2009

ChemotherapyMedian OS

10-11 m

- Succes: Trastuzumab- Doubts: Lapatinib- Hopes: T-DM1, Pertuzumab

3807 scrined pts 810 (21%) HER2+. 584 pts included

97% M1; 32% EGJ; 10% ECOG 2 CX(87%)-/F(13%)-Trast 86mg/kg/3w

P. III TOGA (C-X/F vs C-X/F-Trastuzumab)

CX(87%)/F(13%)

Bang IJ, Lancet 2010

Primary endpoint OS

OS (median) 11.1 m HR 0.74 p 0.004 13.8 mPFS(median) 5.5 m HR 0.71 p 0.0002 6.7 mRR (CR+PR) 34% p 0.001 47%

Chemotherapy

0 5 10 15

EOX (6)XP (7)

ECX (6)ECF (6)DCF (4)EOF (6)

IF (5)CF (4)

FAMTX (2)BSC (1)

Months

C+S1 (3)

1Murad et al 1993; 2Vanhoefer et al 2000; 3Ajani et al 2009;

4Van Cutsem et al 2006; 5Dank et al 2008; 6Cunningham et al 2008; 7Kang et al 2009;

8Van Cutsem et al 2009

Trastuzumab + X/FC (8) HER2 IHC 2+ / FISH+ and IHC 3+

ChemotherapyMedian OS

10-11 m

P III trials with Lapatinib


OS (median) 8.9 m HR 0,84 p 0.20 11 mpts HER-2 IHQ+++ (preplanned analysis)

(median) 7.6 m HR 0,59 p 0.01 14 m

Asia, 2nd line HER2+. 261 pts Taxol-LapatinibTaxol

P. III TYTAN Yung-Jue Bang et al. ASCO-GI 2013

1st líne, HER2+. 540 pts (Asian 40%) CapOx-LapatinibCapOx

P. III LOGIC ASCO 2013

Primary endpoint OS

- OS (median) 10.5 m HR 0,91 p 0.73 12.2 m No better results in en HER-2 IHC+++ OS improvement in asian and <60 y

- PFS (median) 5.4 m HR 0,86 p <0.05 6.8 m

1st líne, HER2+ or EGFR+ 69 pts (planned 350) ECF/X-LapatinibECF/X-Pcb

P. III EORTC 40071 ASCO –GI, 2015

Primary endpoint PFS

- PFS (median) 5.9 m HR 0,94 p NS 7.1 m- OS (median) 10.1 m HR 0,90 p NS 13,8 m


Gastric Cancer: Other anti HER-2T-DM1

Phase II/III GATSBY Taxane-T-DM12nd line Taxane412 pts, HER2 + Primary endpoint: P.II: efficacy, tox

P.III: OS

Ongoing

Mechanism of action


Gastric Cancer: Other anti HER-2: Pertuzumab

Fase III JACOB (NCT01774786) QT-Tratuzumab-Pertuzumab1ª línea QT-Trastuzumab-placebo780 pts, HER2 + Objetivo 1º: Sv

En marcha


-Succes: Ramucirumab, apatinib- Deceptions: Bevacizumab, sorafenib- Hopes: Regorafenib…

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Ramucirumab (IgG1 anti VGFR-2)Two positive P III in second line…

1) Fuchs CS et al. Lancet 2014; 383: 31-9

P. III REGARD 1

Advanced Gastric Adenoca. , 2nd line 355 pts (rand 2/1)

PlaceboRamucirumab 8 mg/kg cada 2 sem

OS (median) 5.2 m HR 0,77 p 0,04 3,8 mDFS(median) 2,1 m HR 0,48 p<0,0001 1,3 mPR+SD 49% p<0,0001 23%

Tox (G 3-4) Ramu / Pcb-Hypertension: 8% 3% -Haemorragia 3,4% 2,6%-Arterial TE 1,7% 0-GI Perforation 0,7% 0

Objetivo 1º: SvPrimary endpoint: OS

Months

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17

Pro

gre

ss

ion

Fre

e S

urv

iva

l

0.0

0.2

0.4

0.6

0.8

1.0

RamucirumabPlaceboCensored

SLPDFS

Ramucirumab (IgG1 anti VGFR-2)Two positive P III in second line …

1) Wilke H et al. Lancet Oncology 2014

P. III RAINBOW 1

Advanced Gastric cancer, 2nd line 665 pts (rand 1/1)

Paclitaxel-placebo

Paclitaxel 80 mg/m2 d 1,8,15

Ramucirumab 8mg/kg d 1, 15 cada 28d

Primary Endpoint:OS

OS (median) 9,6 m HR 0,80 p 0,01 7,3 mDFS(median) 4,4 m HR 0,63 p<0,0001 2,8 mRR 28% p<0,0001 16%PR+SD 80% p<0,0001 64%

CT in advanced Gastric CancerSecond line CT

1.- Thuss-Patience. Eur J Cancer ; 2.- S.H.Park. ASCO-11, # 4004 ; 3.- ASCO 2013, #4023

HR: 0,63

P.III Korean 2: 202 pIrino o Docetaxel vs BSC

1º endpoint: OS

HR 0,63

P. III AIO 1: 40 pIrinotecán vs BSC

1º endpoint: OS

P. III COUGAR-2 3: 168 pDocetaxel vs BSC

1ª endpoint: OS

OS 5,2m vs 3,6 m,HR 0,67, p 0,01

HR: 0,63

Kim H S et al. Ann Oncol 2013;24:2850-2854

CT in advanced Gastric CancerSecond line CT: Meta-analysis

Second line Treatmentin Advanced Gastric Cancer

S Qin et al, ASCO 2014, # 4003

VEGFR TKI: Apatinib

P. III chineseAdvanced Gastric Cancer, 3rd line

273 pts

PlaceboApatinibPrimary endpoint: OSOS (median) 6,5 m HR 0,70 p 0,01 4,7 mDFS(median) 2,6 m HR 0,44 p<0,0001 1,8 mPR+SD 42% p<0,0001 8 %


774 pts 98% M1; 14% EGJ; 5% ECOG 2intestinal 38%, diffuse 50%, mixt 8%Asia 49%, Europe 32%, America 19% CX-Beva 7,5 mg/kg/3s

P. III AVAGAST (CX vs CX-Bevacizumab)

CX-placebo

Van Cutsem E, ESMO 10 #713P; Kang, ASCO 2010 #LBA4007

OS (median) 10,1 m HR 0,87 p 0.10 12,1mDFS (median) 5.3 m HR 0,80 p 0.003 6,7 m(CR+PR) 37% p 0.03 46%No important differences in G 3-4 Toxicity

1º endpoint: OS

DFS



195 pts (asian), 1st lineM1; 15% EGJ; ECOG 0-1

CX-Sorafenib

P. III STARGATE (CX vs CX-Sorafenib)

CX

Kang YK et al, ESMO 2014 #LBA4007

1º endpoint: DFS

OS

DFS (median) 5,3 m HR 0,92 p 0.60 5,6 mOS (median ) 10,8 m HR 0,93 p 0.66 11,7 m(CR+PR) 52% p 0.82 54%


147 pts , 2ª,3ª linea, ECOG 0-1, Rand 2:1Estratificación: Región (37% Asia); líneas previas (1:43%) Placebo

P. II Rand. INTEGRATE (Regorafenib vs placebo)

Regorafenib1600 mg/d, d 1-21 cada 28d

1º endpoint: PFSPFS (median) 2,7 m HR 0,41 p<0.0001 1 mOS (median ) 6,2 m HR 0,68 p 0.06 4,7 m

Pavlakis N et al. ASCO-GI 2015

Prog

OS


- Deceptions: anti-EGFR, everolimus, ¿anti-MET/HGF?

- Hopes: Inmunoterapy…


Cetuximab and PanitumumabTwo negative P III: EXPAND and REAL-3



Everolimus

1) Ohtsu A, et al. J Clin Oncol, 2013

mTOR inhibitor

P. III GRANYTE-1 1Advanced Gastric Cancer, 2nd, 3rd line

656 pts

PlaceboEverolimus Primary endpoint: OS

OS (median) 5.4 m p 0,12 4,3 mDFS(median) 1,7 m p<0,0001 1,4 m



P III RILOMET-1 ECX-Rilotumumab (15 mg/kg)1st line , c-Met +, HER2 - ECX-Placebo609 pts, Primary endpoint: OS Cunningham D, ASCO 2015

Anti HGF/c-Met in Advanced Gastric CancerP III with Rilotumumab and Onartuzumab

P. III METGASTRIC mFOLFOX-Onartuzumab1st line , c-Met +, HER2 - mFOLFOX-placebo560 pts, Primary endpoint: OS Shah MA, ASCO 2015

OS PFS

OS and MetICH

FISH

OS PFS

PFSMet 2+/3+

OSMet 2+/3+

MET

AMG 337)

Anti HGF/c-Met in Advanced Gastric CancerAMG 337 (anti MET TKI)

F I AMG 337 (90 pts)


Kwak EL et al. ASCO-GI 2015

21 pts con C Esof-Gast Av 13 pts MET amplif

Rta: 8/13: 62%

Immunomodulators

Pembrolizumab

P I Pembrolizumab in refractory Advanced Gastric Cancer

Muro K et al, ASCO- 2015

39 pts, (19 asian)Tumours PD-L1 + (40%)RR 22%, PR+SD: 36% (Central Review)


Conclusiones: enfermedad Resecable


Cancer

Gastric Cancer

- Perioperative Chemotherapy- Postoperative Chemo-Radiotherapy- Postoperative Chemotherapy ??


- Succes: Trastuzumab- Doubts: Lapatinib- Hopes: T-DM1, Pertuzumab

-Succes: Ramucirumab, apatinib- Deceptions: Bevacizumab, sorafenib- Hopes: Regorafenib…

- Deceptions: anti-EGFR, everolimus, ¿anti-MET/HGF?

- Hopes: Inmunoterapia…



Gracias

avances en el tratamiento del cáncer gástrico y esofágico€¦ · tratamiento de la enfermedad...

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