746TiP - APACT: A phase III trial of nab-paclitaxel (nab-P) plus gemcitabine (Gem) vs Gem alone for resected pancreatic cancer (PC)

Date 29 September 2014
Event ESMO 2014
Session Poster Display session
Topics Anticancer agents
Pancreatic Cancer
Therapy
Biological Therapy
Presenter Margaret Tempero
Citation Annals of Oncology (2014) 25 (suppl_4): iv210-iv253. 10.1093/annonc/mdu334
Authors M.A. Tempero1, D. Cardin2, A. Biankin3, D. Goldstein4, M. Moore5, E.M. O\'Reilly6, P.A. Philip7, H. Riess8, T. Macarulla9, L. Yung10, X. Wei11, B. Lu10
  • 1Medicine, UCSF Helen Diller Family Comprehensive Cancer Center, 94115 - San Francisco/US
  • 2Medical Oncology, Vanderbilt University Medical Center, Nashville/US
  • 3Oncology, Wolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Glasgow/GB
  • 4Oncology, Prince of Wales Hospital, Sydney/AU
  • 5Oncology, Princess Margaret Hospital, Toronto/CA
  • 6Gastro-intestinal Medical Oncology, Memorial Sloan-Kettering Cancer Center, US-10128 - New York/US
  • 7Oncology, Karmanos Cancer Center, 48201 - Detroit/US
  • 8Oncology, Charité-Universitätsmedizin Berlin, Campus Virchow-Klinikum, DE-13353 - Berlin/DE
  • 9Oncology, Vall d´Hebron University Hospital, 08035 - Barcelona/ES
  • 10Clinical Research, Celgene Corporation, Summit/US
  • 11Biostatistics, Celgene Corporation, Summit/US

Abstract

Background

Gem monotherapy after surgery improves both survival rates and disease-free survival (DFS) in patients with PC. However, disease recurrence is common, suggesting a need for improved regimens. nab-P + Gem demonstrated superior efficacy to Gem alone in a phase III metastatic PC trial, including the primary endpoint of overall survival (OS [8.7 vs 6.6 months; hazard ratio (HR) 0.72; P < 0.001]). Toxicities were manageable. Based on the activity demonstrated in the metastatic setting, nab-P + Gem will be compared with Gem alone in the adjuvant setting.

Trial design

Approximately 800 patients with histologically confirmed pancreatic cancer who undergo macroscopic complete resection (R0 or R1), with no evidence of metastasis, will be randomized 1:1 to receive 6 cycles of either nab-P 125 mg/m2 plus Gem 1000 mg/m2 or Gem alone 1000 mg/m2 days 1, 8, and 15 of each 28-day cycle. Other eligibility criteria include staging T1-3, N0-1, M0; ECOG PS 0 or 1; acceptable hematologic function; CA19-9 < 100 U/mL prior to randomization, and no prior neoadjuvant therapy or radiation for PDA. Patients with neuroendocrine tumors, any other malignancy within 5 years of randomization, HIV infection, hepatitis B or C infection, or prior neoadjuvant treatment or radiation therapy for PC are ineligible. Stratification factors are resection status (R0 vs R1), nodal status (LN+ vs LN−), and geographic region (North America, Europe, and Australia vs Asia Pacific). The primary endpoint is independently assessed DFS and secondary endpoints are OS and safety. Exploratory endpoints include molecular profiling of tumor tissue to correlate tumor heterogeneity with clinical outcome and quality of life as assessed by the European Organisation for the Research and Treatment of Cancer Quality of Life Questionnaires–C30 and PAN26. The planned enrollment of 800 patients will allow 90% power to detect an HR for DFS of 0.74 at a 2-sided significance level of 0.05. One interim safety analysis and 2 interim efficacy analyses (the first for futility and the second for both futility and efficacy) will be performed. Patient enrollment is ongoing. Clinical trial NCT01964430.

Disclosure

M.A. Tempero: Consultant or advisory role and research funding, Celgene; A. Biankin: Consultant or advisory role, Celgene; D. Goldstein: Consultant of advisory role unremunerated and research funding, Celgene; M. Moore: Consultant of advisory role and honoraria, Celgene; E.M. O'Reilly: Consultant or advisory role, Celgene; P.A. Philip: Consultant: BMS, Bayer/Onyx, SA, Curis, Lilly, Amgen, Clovis, BI, GHI, Roche, Gilead, NVS, TLOG; Honoraria: Amgen, NVS, GNE, Bayer/Onyx, Roche, SA, Celgene; Research funding: GNE, BMS, NVS, Genvec, Chugai, Nektar, Amgen, Lilly, Roche, Bayer, Incyte, SA; H. Riess: Consultant or advisory role, Celgene; L. Yung, X. Wei and B. Lu: Employment or leadership position and stock ownership, Celgene. All other authors have declared no conflicts of interest.