what's new in oral chemotherapy - ncoda · what’s new with oral chemotherapy? national...

Fall Summit | October 18-20 | Orlando, FL

Sarah Peters, PharmD, MPH, BCOP, Associate Professor, Pharmacy Practice, Albany College of Pharmacy and Health

Sciences

What's New in Oral Chemotherapy

What’s new with Oral Chemotherapy? NATIONAL COMMUNITY ONCOLOGY DISPENSING ASSOCIATION NATIONAL SUMM IT

OC TOBER 20, 2017 – ORLANDO, FL

SARAH SCARPACE PETERS , PHARMD, MPH, BCOP

ASSOCIATE PROFESSOR, PHARMACY PRAC TICE

ALBANY COLLEGE OF PHARMACY AND HEALTH SC IENCES

2

Pharmacist objectives 1. Describe the mechanism of action of new therapies

2. Counsel on the side effect profile of new therapies

3. Identify the place in therapy of oral chemotherapy in cancer treatment

3

Pharmacy Technician objectives 1. Identify new oral oncology agents that have recently been FDA-

approved

2. Identify the type of cancer new oral chemotherapy agents will treat

3. Understand the importance of the gradual transition from IV chemotherapy to oral chemotherapy

4

Overview Timeline of 2017 FDA oral chemotherapy drug indications for existing drugs (5 + 2 new drugs for benign heme)

Detailed review of new drugs approved by the FDA in 2017 ◦ Acute myeloid leukemia (2)

◦ Lung cancer (1 “.5”)

◦ Ovarian cancer (2 “.5”)

◦ Breast cancer (2)

Summary

5

Old drugs, new indications FDA APPROVALS IN 2017 FOR ORAL CHEMO DRUGS ALREADY ON THE MARKET….

6

2017 New FDA indications for old drugs

7

January June December October

2/22: lenalidomide maintenance s/p transplant

3/30: osimertinib regular approval T790M met. lung 2nd line 3/31 palbociclib regular approval HR+/HER2- met. breast with AI

6/22: dabrafenib/tremetinib regular approval V600E BRAF met. Lung 1st line

8/2: ibrutinib breakthrough/orphan drug for GVHD

6/23: betrixaban for VTE prophy in hospitalized patients

7/7 L-glutamate powder for sickle cell anemia

U.S. Food and Drug Administration. Drugs@FDA: FDA Approved Drug Products. Drug approval reports by month. Available from: https://www.accessdata.fda.gov/scripts/cder/daf/. Accessed 9/22/2017.

And some new drugs for benign heme…

https://www.accessdata.fda.gov/scripts/cder/daf/


NEW! Oral chemo drugs FDA APPROVALS FOR NOVEL ORAL CHEMO DRUGS IN 2017

8

2017 FDA Approvals for New Drugs

9

January June December October

12/19/16 Rucaparib accelerated approval g/s-BRCA ovarian 3rd+ line

3/13 ribociclib + AI HR+/HER2- met. Breast 1st line

7/17 neratinib for HER2+ early breast s/p adjuvant trastuzumab

8/1 enasidenib for adults with IDH2mutated r/r AML

U.S. Food and Drug Administration. Drugs@FDA: FDA Approved Drug Products. Drug approval reports by month. Available from: https://www.accessdata.fda.gov/scripts/cder/daf/. Accessed 9/22/2017.

3/27 niraparib maintenance for met. Ovarian s/p CR or PR to platinum

4/27 lorlatinib breakthrough ALK/ROS1+ met. NSCLC s/p another ALK therapy 4/28 brigatinib orphan drug for ALK+ NSCLC s/p crizotinib 4/28 midostaurin ASM, SM-AHN, MCL, and FLT3+ AML with 7+3 regimen

8/17 olaparib tablet formulation



Acute Myeloid Leukemia ENASIDENIB

MIDOSTAURIN

10

FDA Indications

ENASIDENIB (IHDFA ®)

IDH2 mutation positive AML

MIDOSTAURIN (RYDAPT ®)

Aggressive systemic mastocytosis (ASM)

Systemic mastocytosis with associated hematological neoplasm (SM-AHN)

Mast cell leukemia (MCL)

FLT3+ AML with the 7+3 regimen

11

Isocitrate dehydrogenase 1 and 2

citrate

aconitrate

isocitrate Alpha -

ketoglutarate

Et cetera

12

Isocitrate dehydrogenase

Mutated isocitrate dehydrogenase

2-hydroxyglutarate

Kreb’s Cycle

Mutated isocitrate dehydrogenase

LESS

Dang L et al. Nature 2009; 462 (7274): 739-744

IDH2 mutations

occur in about 12% of all AML patients

Isocitrate dehydrogenase 1 and 2

Progenitor cells

Terminally differentiated

cells

13

Histone + CH3

histone

Isocitrate dehydrogenase

Normal IDH1/2 demethylates

progenitor cells to promote

differentiation Mutated isocitrate dehydrogenase

Mutated IDH1/2 prevents

differentiation and promotes cell proliferation

Lu C et al. Nature 2012; 482 (7390): 474-478.

NCT 01915498 Study Design

14

Phase 1/2 Primary Endpoint: safety, MTD N = 239 USA, France, UK Advanced r/r AML or MDS with RAEB IDH2 mutation positive ECOG 0 – 2

5 dose levels at BID

8 dose levels at once daily

Dose Escalation Serum 2-

hydroxyglutarate levels

Serum drug levels

Efficacy by investigator review of peripheral blood and bone marrow samples

Stein EM et al. Blood 2017; 130(6): 722-731.

Enasidenib 100 mg once daily selected for

expansion phase

Efficacy Outcomes

15

Overall Response Rate = 40.3%

Median Response duration = 5.8 months

Median Overall Survival = 9.3 months

Stein EM et al. Blood 2017; 130(6): 722-731.

Side effects – grade 3 or 4

0%

1%

2%

3%

4%

5%

6%

7%

8%

9%

Most Common Side Effects

Treatment-related adverse events

Hyperbilirubinemia Retinoic acid syndrome Anemia Thrombocytopenia Tumore Lysis Syndrome Decreased appetite

16 Stein EM et al. Blood 2017; 130(6): 722-731.

FDA Indications

ENASIDENIB (IHDFA ®)

IDH2 mutation positive AML

MIDOSTAURIN (RYDAPT ®)

Aggressive systemic mastocytosis (ASM)

Systemic mastocytosis with associated hematological neoplasm (SM-AHN)

Mast cell leukemia (MCL)

FLT3+ AML with the 7+3 regimen

17

Midostaurin Mechanism of Action Multikinase inhibitor

FLT3 –both wild type and mutant

KIT – both wild and D816V mutant

PDGFR alpha/beta

VEGFR 2

Protein kinase C family (serine/threonine PKC)

18 Rydapt [package insert]. Novartis; East Hanover, NJ; April 2017

RATIFY/CALGB 10603 Study Design

19

Phase 3 Primary Endpoint: OS N = 717 in 17 countries Newly diagnosed AML FLT3 point mutations in tyrosine kinase

domain or FLT3 internal tandem duplication mutation

Age 18 - 59 Hydroxyurea allowed 5 days pre-entry No concomitant meds that prolong QT or

QT interval >500 msec

Midostaurin 50 mg BID x 14 days days 8-21 q28days + standard 7+3 chemotherapy

Placebo on midostaurin schedule + standard 7+3 chemotherapy

Randomized

Double-Blind Bone marrow day

21 of cycle 1 of induction; if 2nd cycle of induction if needed

4 cycles of consolidation if CR after induction

If remission after consolidation, maintenance midostaurin or placebo for 12 more cycles

Transplant not required but allowed

1:1

*two 25 mg capsules

Stone RM et al. New Engl J Med 2017; 377: 454-464

Stone RM et al. N Engl J Med 2017;377:454-464

Overall Survival

Median OS = 74.7 months Midostaurin versus 25.6 months placebo

ALK mutation+ metastatic NSCLC BRIGATINIB (FDA-APPROVED)

LORLATINIB (NOT FDA-APPROVED BUT BREAKTHROUGH THERAPY DESIGNATION BY FDA)

21

FDA Indications

BRIGATINIB (ALUNBRIG ®)

ALK+ NSCLC s/p crizotinib (orphan drug)

LORLATINIB *NOT FDA APPROVED

Breakthrough status for ALK+ NSCLC s/p 1 or more ALK therapies

22

ALTA-1L Study Design

23

Phase 2 Primary Endpoint: Overall Response Rate N = 222 18 countries Locally advanced or metastatic NSCLC ALK+ Refractory to crizotinib No other ALK-directed therapies ECOG 0 – 2 No pulmonary interstitial disease No drug-related pneumonitis No unstable brain mets

Brigatinib 90 mg once daily

Brigatinib 90 mg once daily x 7 days then 180 mg daily

Randomized

Open-label

Disease assessment q8 weeks through cycle 15 (28 day cycles) then q 12 weeks until progression

Days 8 and 15 pulmonary symptom assessment

1:1

Kim DW et al. J Clin Oncol 2017; 35 (22): 2490-2498

Efficacy Outcomes OVERALL RESPONSE RATE

0%

20%

40%

60%

ORR

90 mg daily

90 mg daily x 7 days then 180 mg daily

MEDIAN PROGRESSION-FREE SURVIVAL

0

5

10

15

PFS (months)

90 mg daily


24

Investigator-assessed

Kim DW et al. J Clin Oncol 2017; 35 (22): 2490-2498

Adverse Events (Any Grade) Brigatinib 90 mg daily x 7 days then 180 mg daily

40% 38%

34%

30%

27%

23% 21%

0%

5%

10%

15%

20%

25%

30%

35%

40%

45%

Any Grade

Nausea Diarrhea Cough Increased CPK2 Fatigue Vomiting Hypertension

Grade 3/4 over 2%: Increased CPK (9%); Hypertension (6%); Rash (3%); 2%: dyspnea and back pain

25 Kim DW et al. J Clin Oncol 2017; 35 (22): 2490-2498

Ovarian Cancer (metastatic) R UCA PA R I B

N I R A PA RI B

OLA PA R IB TA BLETS

26

FDA Indications

Olaparib (Lynparza ®) Rucaparib (Rubraca ®) Niraparib (Zejula ®)

• maintenance treatment • recurrent epithelial ovarian,

fallopian tube, or primary peritoneal cancer

• complete or partial response to platinum-based chemotherapy

• maintenance treatment • recurrent epithelial ovarian,

fallopian tube, or primary peritoneal cancer

• complete or partial response to platinum-based chemotherapy

deleterious or suspected deleterious germline BRCA-mutated advanced ovarian cancer who have been treated with three or more prior lines of chemotherapy.

deleterious BRCA mutation (germline and/or somatic) associated advanced ovarian cancer who have been treated with two or more chemotherapies.

27

Lynparza [package insert]. Wilmington, DE: Astra-Zeneca; August 2017

Zejula [package insert]. Waltham, MA: Tesaro; March 2017 Rubraca [package insert]. Boulder, CO: Clovis Oncology, Inc; December 2016

Synthetic Lethality and BRCA

28 Ashworth A. A synthetic lethal therapeutic approach: poly (ADP) ribose polymerase inhibitors for the treatment of cancers deficient in DNA double-strand break repair. J Clin Oncol 2008; 26(22): 3785-3790

Homologous repair mechanism are standard way normal cells repair double-strand breaks in DNA

Alternative repair mechanisms, such as non-homologous end-joining or single-strand annealing are used in the absence of BRCA1 or BRCA2

PARP-1 inhibition blocks single-strand break repair but not double-strand break repair

Synthetic Lethality

29

Gene 1 Gene 2 Outcome of Drug Therapy

No mutation No Mutation No effect

No mutation Mutation No effect

Mutation No Mutation No effect

Mutation Mutation Effect

When drug therapy works when only both genes of a pair are defective, there is a larger therapeutic window -PARP inhibitors won’t interfere with DNA repair in those cells that are heterozygous for BRCA mutations or which have normal BRCA genes (ie., the noncancerous cells)

Ashworth A. A synthetic lethal therapeutic approach: poly (ADP) ribose polymerase inhibitors for the treatment of cancers deficient in DNA double-strand break repair. J Clin Oncol 2008; 26(22): 3785-3790

Clinical Trials Olaparib Rucaparib Niraparib

Name of study SOLO-2 Study 19 ARIEL2 Part 1 NOVA/ ENGOT-OV16

Phase 3 2 2 3

Randomized Yes Yes No Yes

Double-blind Yes Yes No Yes

Placebo-controlled Yes Yes No Yes

Sample size 295 265 206 553

Role of BRCA germline Irrespective Somatic, germline, or none

Germline BRCA vs. not

Disease Relapsed, platinum-sensitive

Recurrent, platinum-sensitive

Recurrent, platinum-sensitive, high-grade

Recurrent, platinum-sensitive, high grade

Prior therapies 2 prior platinums 2 prior platinums 1 or 2 platinums 2 prior platinums

Intervention 300 mg BID 400 mg BID 600 mg BID 300 mg once daily

Primary Endpoint PFS PFS PFS PFS

30 Swisher EM et al. Lancet Oncol 2017; 18: 75-87 Mirza MR et al. N Engl J Med 2016; 375 (22): 2154-2164

Pujade-Lauraine E et al. Lancet Oncol 2017; 18(9): 1274-1284.

Ledermann JA et al. Lancet Oncol 2016; 17(11): 1579-1589. Kaufman B, Shapira-Frommer R, Schmutzler RK, et al. J Clin Oncol 2015; 33 93): 244-250.

PFS (months)



Ledermann JA et al. Lancet Oncol 2016; 17(11): 1579-1589.

19.1

0

7

0

12.8

5.7

21

12.9

0

5

10

15

20

25

gBRCA nonBRCA olaparib SOLO2 Olaparib Study 19 Rucaparib ARIEL2 niraparib NOVA

BRCA-mutated BRCA wild-type

Note Olaparib Study 19 did not meet threshold for statistical significance for follow-up of Overall Survival in both BRCA(set at p<0.0095; p = 0.025) and non-BRCA patients

Adverse Events – Overall

76%

66%

43% 38%

33%

15%

21%

79% 78%

36%

44%

33%

14%

46%

73.60%

59.40%

50.10%

36.20%

19.40%

61.30%

39.80%

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

Nausea Fatigue RBC Vomiting Diarrhea PLT Constipation

Olaparib SOLO-2 Rucaparib Niraparib



Adverse Events – Grade 3 or 4

1%

19%

5%

0

4%

0

22%

12%

33.80%

25.30%

19.60%

8.20% 8.20%

0 0%

5%

10%

15%

20%

25%

30%

35%

40%

PLT RBC WBC Hypertension Fatige LFTs

Olaparib SOLO-2 Rucaparib Niraparib



Breast Cancer R I BOCI CL I B N ER AT I N IB FOR H ER 2+ EA R LY STAGE BR EA ST CA N CER A FT ER A DJUVA N T T R A ST UZ UM A B

34

FDA Indications

RIBOCICLIB (KISQALI®)

HR+/HER2- advanced or metastatic breast cancer with an Aromatase inhibitor

NERATINIB(NERLYNX ®)

Extended adjuvant treatment of early stage breast cancer after trastuzumab adjuvant therapy

35 Nerlynx [package insert]. Los Angeles, CA: Puma Biotechnology, Inc; July 2017. Kysqali [package insert]. East Hanover, NJ: Novartis Pharmaceuticals Corporation; March 2017.

ABEMACICLIB (VERZENIO®)

HR+/HER2- advanced or metastatic breast cancer with fulvestrant after endocrine therapy

HR+/HER2- advanced or metastatic breast cancer in women and men as monotherapy after endocrine therapy and chemotherapy

Verzenio [package insert]. Indianapolis, IN: Eli Lilly & Co; September 2017

cdk pathway

36

Cyclin-dependent kinases promote progression from G1 phase to S phase by phosphorylating retinoblastoma protein

Shapiro GI. Cyclin-dependent kinase pathways as targets for cancer treatment. J Clin Oncol 2006; 24(11): 1770-1783.

G2 phase – growth, DNA

repair, preparation for division

M phase – mitosis/ cell

division

G1 phase – growth and

normal metabolic functions

S phase – DNA

replication

Retinoblastoma protein

Cyclin dependent kinase

Phosphorus

Study Designs MONALEESA 2 MONARCH 2 MONARCH 1

Phase 3 3 2

R, PC, DB Yes Yes No (open-label, single arm)

Primary Endpoint PFS PFS Objective Response Rate

Population HR+/HER2-, recurrent/metastatic

HR+/HER2-, advanced breast cancer HR+/HER2- metastatic breast cancer

Prior therapies None Neoadj. Or adjuvant endocrine therapy

Endocrine therapy and 1 or 2 chemotherapies

Notes No concomitant QT interval-prolonging meds

Protocol amended after safety review to lower dose from 200 mg BID to 150 mg BID

Intervention Ribociclib 600 mg (three 200 mg capsules) daily days 1-21 q 28 days + letrozole 2.5 mg daily

Abemaciclib 150 mg BID + fulvestrant 500 mg IM days 1, 15 cycle 1 then day 1 q 28 days

Abemaciclib 200 mg BID

37 Hortobagyi GN et al. N Engl J Med 2016; 375(18): 1738-1748.

Sledge GW et al. J Clin Oncol 2017; 35(25): 2875-2884. Dickler MN. Clin Cancer Res 2017; 23(17): 5218-5224

MONALEESA-2 PFS

Hortobagyi GN et al. N Engl J Med 2016;375:1738-1748

Median PFS not reached in ribociclib arm at time of interim analysis; median PFS in placebo arm = 14.7 months

18-months PFS rate was 63% in ribociclib arm vs. 42.2% in placebo arm

0%

10%

20%

30%

40%

50%

60%

70%

18-month PFS

Ribociclib Placebo

HR = 0.56 (95% CI, 0.43 – 0.71; p = 3.92 x 10-6)

MONARCH 2 PFS

HR = 0.553 (95% CI, 0.449 – 0.681) 16.4

9.3

0

2

4

6

8

10

12

14

16

18

median PFS (months)

abemaciclib + fulvestrant placebo + fulvestrant

Sledge GW et al. J Clin Oncol 2017; 35(25): 2875-2884.

MONARCH 1

Dickler MN. Clin Cancer Res 2017; 23(17): 5218-5224

Result

Objective Response Rate 19.7% (95% CI, 13.3 – 27.5%)

PFS (median) 6 months

OS (median) 17.7 months

Adverse Events – All Grades Selected most common

74.3

51.5 50.3 36.5 35 33.2 29.3 27.2 24.9

46 45.1 42.6 39.9

86.4

15.6 25.9

11.6 13.6

0

20

40

60

80

100

letrozole + ribociclib abemaciclib + fulvestrant

41

% O

F PA

TIEN

TS

Hortobagyi GN, Stemmer SM, Burris HA, et al. Ribociclib as first-line therapy for HR-positive, advanced breast cancer. N Engl J Med 2016; 375(18): 1738-1748.


Adverse Events – Grade 3/4 Selected most common

59.3

1.2 1.2 2.4 4.2 9.3 5.7

26.5

13.4 7.2 2.7 6.6 2.3 4.1

0 10 20 30 40 50 60 70

letrozole + ribociclib abemaciclib + fulvestrant

42

% O

F PA

TIEN

TS

Febrile neutropenia = 1.5% in letrozole + ribociclib vs. none in letrozole + placebo Febrile neutropenia = 0.009% in abemaciclib + fulvestrant vs. none in fulvestrant + placebo

Hortobagyi GN, Stemmer SM, Burris HA, et al. Ribociclib as first-line therapy for HR-positive, advanced breast cancer. N Engl J Med 2016; 375(18): 1738-1748.


FDA Indications

RIBOCICLIB (KISQALI®)

HR+/HER2- advanced or metastatic breast cancer with an Aromatase inhibitor

NERATINIB(NERLYNX ®)

Extended adjuvant treatment of early stage breast cancer after trastuzumab adjuvant therapy

43 Nerlynx [package insert]. Los Angeles, CA: Puma Biotechnology, Inc; July 2017. Kysqali [package insert]. East Hanover, NJ: Novartis Pharmaceuticals Corporation; March 2017.

ABEMACICLIB (VERZENIO®)

HR+/HER2- advanced or metastatic breast cancer with fulvestrant after endocrine therapy

HR+/HER2- advanced or metastatic breast cancer in women and men as monotherapy after endocrine therapy and chemotherapy

Verzenio [package insert]. Indianapolis, IN: Eli Lilly & Co; September 2017

ExteNET Study Design

44

Phase 3 Primary Endpoint: invasive DFS N = 2840 Europe, Asia, Australia, NZ, NA, SA Early stage HER2+ breast cancer after

neoadj. and adj. trastuzumab Initially Stage 1- 3, node positive or

negative and trastuzumab completed up to 2 years prior

Later Stage 2-3, node positive only and tras within 1 year

Neratinib 240 mg once daily

Matching Placebo daily

Randomized

Double-blind

Disease assessment q8 weeks through cycle 15 (28 day cycles) then q 12 weeks until progression

Days 8 and 15 pulmonary symptom assessment

1:1

Chan A et al. Lancet Oncol 2016; 17: 367-377

Protocol was amended 5 times!

ExteNET 2-year DFS 93.90%

91.00%

0.00%

10.00%

20.00%

30.00%

40.00%

50.00%

60.00%

70.00%

80.00%

90.00%

100.00%

2-year DFS

Neratinib Placebo

45 Chan A et al. Lancet Oncol 2016; 17: 367-377

HR = 0.67; (95% CI, 0.50 – 0.91)

ExteNET Adverse Events

96%

41% 43%

2%

27%

2%

26%

3%

24%

2%

20%

1%

16%

1% 0%

20%

40%

60%

80%

100%

120%

Any Grade Grade 3/4

Diarrhea Nausea Fatigue Vomiting Abdominal Pain Headache Rash

46 Chan A et al. Lancet Oncol 2016; 17: 367-377

Practical information Dose & Schedule

Pills/dose With food?

pH -dependent absorption

Renal/ Hepatic Adjustments

CYP drug interactions

QT interval issues

Top 5 Side Effects

Enasidenib (Idhifa®) Warning: Differentiation syndrome

100 mg daily

One tablet

Doesn’t matter

no None/unknown severe renal/hepatic

1A2, 2B6, 2C8, 2C9, 2C19, 2D6, 3A4, UGT1A1, pgp, inhibitor; 2D6 and 3A4 inducer

No Nausea; vomiting; diarrhea; elevated bili; decreased appetite

Midostaurin*

(Rydapt ®) Warning: Pulmonary toxicity

50 mg (AML) or 100 mg BID

Two or Four 25 mg capsules

Yes + antiemetic

No None 3A4 substrate Yes Nausea; vomiting; diarrhea; edema; fatigue

Brigatinib (Alunbrig®) Warnings: ILD, htn; cpk; pancreatitis; glucose; vision


One or two 90 mg capsules

Doesn’t matter

No No 3A substrate and inducer

No Nausea; diarrhea; fatigue; cough; headache 47

*for drug alone in non-AML patients

None should be used in pregnancy!


Pills/dose With food? pH –absorb?

Renal/ Hepatic


QT interval issues

Top 5 Side Effects

Niraparib (Zejula ®) warning: htn, HR, myelo-suppression

300 mg once daily

Three 100 mg capsules

Doesn’t matter

No No though unknown in severe renal/hepatic

None PgP substrate

None Nausea; PLT; fatigue; RBC; constipation

Rucaparib (Rubraca®)

600 mg BID

Two 200 mg capsules

Doesn’t matter

No No though unknown in severe renal/hepatic

(in vitro) 1A2, 2C9, 2C19,3A4 inhibitor; 1A2 inducer

None Nausea; fatigue; constipation; vomiting; LFTs

Olaparib (Lynparza®) Warning: pneumonitis

300 mg TABLET BID

Two 150 mg TABLETS

Doesn’t matter

No Reduce CrCl<60

3A4 substrate

None Nausea; fatigue; RBC; vomiting; diarrhea

48

All PARP inhibitors have a warning about risk of myelodysplastic syndrome



Pills/dose With food? pH -dependent absorption

Renal/ Hepatic


QT interval issues

Top 5 Side Effects

Ribociclib (Kisqali®) Warning: QT, bili, neutropenia

600 mg days 1-21 q 28d

Three 200 mg tablets

Doesn’t matter

No Neither 3A4 substrate Probably Neutropenia; nausea; fatigue; diarrhea; alopecia

Abemaciclib (Verzenio®) Warning: diarrhea, neutropenia, LFTs, VTE

150 mg BID with fulvestrant or 200 mg BID alone

One 150 mg or 200 mg tablets

Doesn’t matter

No Severe hepatic; not known for CrCl<30

3A4 substrate No Diarrhea; neutropenia; nausea; abdominal pain; infections

Neratinib (Nerlynx®) Warning: diarrhea, LFTs

240 mg daily x 1year with prophylactic antidiarrheal cycles 1-2

Six 40 mg tablets

Yes Yes Severe hepatic

3A4 substrate; PgP inhibitor

No Diarrhea; nausea; fatigue; abdominal pain; headache 49


Questions?

Thank you for your time and the opportunity to present!

50

what's new in oral chemotherapy - ncoda · what’s new with oral chemotherapy? national...

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