apact: phase iii, multicenter, international, open-label

Presented By Margaret Tempero at 2019 ASCO Annual Meeting

APACT: Phase III, Multicenter, International, Open-Label, Randomized Trial of Adjuvant nab®-Paclitaxel Plus Gemcitabine vs Gemcitabine for Surgically ResectedPancreatic Adenocarcinoma

Margaret A. Tempero,1 Michele Reni, 2 Hanno Riess, 3 Uwe Pelzer, 3 Eileen M. O’Reilly, 4 Jordan Winter, 5

Do-Youn Oh, 6 Chung-Pin Li, 7 Giampaolo Tortora, 8,9 Heung-Moon Chang, 10 Charles D. Lopez, 11

Josep Tabernero, 12 Eric Van Cutsem, 13 Philip Philip, 14 David Goldstein, 15 Jordan D. Berlin, 16

Stefano Ferrara, 17 Mingyu Li, 17 Brian Lu, 17 Andrew Biankin18

1University of California, San Francisco, Helen Diller Comprehensive Cancer Center, San Francisco, CA; 2IRCCSOspedale San Raffaele, Milan, Italy; 3Charité-UniversitätsmedizinBerlin, Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, Berlin, Germany; 4MemorialSloan Kettering Cancer Center, New York City, NY; 5Thomas Jefferson University Hospital, Philadelphia, PA; 6Seoul National University Hospital, CancerResearch Institute, Seoul National University College of Medicine, Seoul, South Korea; 7Taipei Veterans General Hospital, Taipei, Taiwan; 8Azienda Ospedaliera Universitaria, Verona, Italy; 9Fondazione Policlinico Universitario Gemelli, IRCCS, Rome, Italy; 10Asan Medical Center, Seoul, South Korea; 11Oregon Health and Science University, Portland, OR; 12Vall d’Hebron University Hospital and Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain; 13University Hospitals Gasthuisberg/Leuven and KU Leuven, Leuven, Belgium; 14Karmanos Cancer Institute, Detroit, MI; 15Nelune Cancer Centre, Prince of Wales Hospital, University of New South Wales, Randwick, NSW, Australia; 16Vanderbilt-Ingram Cancer Center, Nashville, TN; 17Celgene Corporation, Summit, NJ; 18University of Glasgow, Glasgow, Scotland

nab®is a registered trademark of Celgene Corporation.


Introduction

a Primary endpoint.

• Pancreatic cancer (PC) is a leading cause of cancer-related death globally (5-year survival rate, < 10%)1-3

• Adjuvant chemotherapy has improved survival outcomes in resected PC

• The phase III MPACT trial demonstrated significantly longer OS with nab-P + Gem vs Gem alone in metastatic PC (median OS, 8.7 vs 6.6 months; P < 0.001)4

• The APACT trial assessed the efficacy and safety of adjuvant nab-P + Gem vs Gem alone in patients with surgically resected PC

• Since APACT was launched, Gem + Cape and mFOLFIRINOX became preferred category 1 recommendations for adjuvant PC according to National Comprehensive Cancer Network guidelines5

1. American Cancer Society. Global cancer facts & figures. 4th ed. Atlanta, GA: American Cancer Society, 2018. 2. Ducreux M, et al. Ann Oncol. 2015;26 (suppl 5):v56-v68. 3. Surveillance, Epidemiology, and End ResultsProgram. Cancer stat facts: pancreatic cancer. https://seer.cancer.gov/statfacts/html/pancreas.html. Published 2018. Accessed April 12, 2019. 4. Goldstein D, et al. J Natl Cancer Inst.2015;107:doi:10.1093/jnci/dju413. 5. NCCN Clinical Practice Guidelines in Oncology. Pancreatic Adenocarcinoma. V1.2019. 6. Neoptolemos JP, et al. Lancet. 2017; 389:1011-1024. 7. Conroy T, et al. N Engl J Med. 2018;379:2395-2406.

DFS, disease-free survival; mFOLFIRINOX, modified FOLFIRINOX (leucovorin, fluorouracil, irinotecan, and oxaliplatin); OS, overall survival; RFS, relapse-free survival.


Study Design

APACT: phase III, multicenter, international, open-label, randomized trial

• Patients were randomized as early as possible after adequate recovery from surgery but no later than 12 weeks after surgery

• Stratification factors: resection status (R0 vs R1); lymph node status (LN+ vs LN–); geographic region (North America, Europe and Australia vs Asia Pacific)

CA19-9, carbohydrate antigen 19-9; ECOGPS, Eastern Cooperative Oncology Group performance status; LN, lymph node; PDAC, pancreatic ductal adenocarcinoma; qw 3/4, the first 3 of 4 weeks; R0/R1, macroscopic complete resection with tumor-free/microscopically positive margin.aNeoadjuvant, radiation, or systemic therapy.

Patients ≥ 18 y of age with confirmed

resected PDAC(T1-3, N0-1,M0);

R0/R1; ECOG PS 0or 1; CT without

evidence of disease CA19-9 <100

U / m L ; no pr ior therapya

Arm Anab-P 125 mg/m2 qw 3/4+ Gem 1000 mg/m2 qw 3/4

x 6 cyclesEnd of treatment Treat for 6 cycles

unless recurrence, death, unacceptable

toxicity, consent withdrawal, or

patient/physician decision

Ran

dom

ized

1:1

Arm B

Gem 1000 mg/m2 qw3/4x 6 cycles

Follow-upRadiological evaluation

for ≤ 5 years afterlast dose or until

recurrence, new cancertherapy, or death;

safety assessment for28 days after last dose


Primary Endpoint:Independently Assessed DFS (ITT Population)

Median independently assessed DFSnab-P + Gem: 19.4 monthsGem: 18.8 months(HR 0.88; 95% Cl, 0.729 - 1.063; stratified log-rank P = 0.1824) Number of events: 439


Prespecified Sensitivity Analysis:Investigator Assessed DFS (ITT Population)

• The concordance rate between disease recurrence by independent radiological review and by investigator review was 77%

Median investigator assessed DFSnab-P + Gem: 16.6 moGem: 13.7 mo(HR 0.82; 95% Cl, 0.694 - 0.965; nominal P = 0.0168) Number of events: 571


Secondary Endpoint:Interim OS (ITT Population)

Median interim OS (68% mature)nab-P + Gem: 40.5 moGem: 36.2 mo(HR 0.82; 95% Cl, 0.680 - 0.996; nominal P = 0.045) Number of events: 427; Median follow-up, 38.5 months


Prespecified Subgroup Analysis:OS (ITT Population)


Safety (Treated Population)

• TEAEs led to death in 2 patients in each arm• Ten patients (16%) with grade ≥ 3 peripheral neuropathy improved to grade ≤ 1• The incidence of TEAEs of special interest–gastrointestinal events, hepatic toxicity, and sepsis–was generally low in both arms

MedDRA, Medical Dictionary for Regulatory Activities; SMQ, standardized MedDRA query; TEAE, treatment-emergent adverse event.a Reported as a group term.


1. Von Hoff DD, et al. N Engl J Med. 2013; 369:1691-1703.

• The primary endpoint of independently assessed DFS was not met

– APACT is the first trial of adjuvant therapy in PC to use independently assessed DFS

– Investigator-assessed DFS aligned more closely with OS results than independently assessed DFS

• Consistent with other trials, the survival with Gem monotherapy was markedly improved, suggesting better patient selection and benefit from treatment with contemporarytherapies upon recurrence of disease

• The nab-P + Gem safety profile was consistent with what was observed in the MPACT trial1

• Results of ongoing biomarker and QoL analyses will be presented at future meetings

• Final OS data will clarify the role for adjuvant nab-P + Gem in resected PC

– Continued investigation of the regimen (eg, in patients with positive lymph nodes or R1 resection as wellas those who are not candidates for FOLFIRINOX) is warranted

Conclusions

apact: phase iii, multicenter, international, open-label

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