106143-133

Randomized phase III study of weekly nab-paclitaxel plus gemcitabine versus gemcitabine alone in patients with metastatic adenocarcinoma of the pancreas (MPACT).

Category: 
Cancers of the Pancreas Small Bowel and Hepatobiliary Tract
Session Type and Session Title: 
General Poster Session B: Cancers of the Pancreas, Small Bowel, and Hepatobiliary Tract
Oral Abstract Session: Cancers of the Pancreas, Small Bowel, and Hepatobiliary Tract (eQ&A)
Abstract Number: 
LBA148
Citation: 
J Clin Oncol 31, 2013 (suppl 4; abstr LBA148)
Author(s): 
Daniel D. Von Hoff, Thomas J. Ervin, Francis P. Arena, E. Gabriela Chiorean, Jeffrey R. Infante, Malcolm J. Moore, Thomas E. Seay, Sergei Tjulandin, Wen Wee Ma, Mansoor N. Saleh, Marion Harris, Michele Reni, Ramesh K. Ramanathan, Josep Tabernero, Manuel Hidalgo, Eric Van Cutsem, David Goldstein, Xinyu Wei, Jose Luis Iglesias, Markus Frederic Renschler; Virginia G. Piper Cancer Center at Scottsdale Healthcare/TGen, Scottsdale, AZ; Florida Cancer Specialists, Englewood, FL; Arena Onc Associates, Success, NY; Indiana University Melvin and Bren Simon Cancer Center, Indianapolis, IN; The Sarah Cannon Cancer Center, Nashville, TN; Princess Margaret Hospital and University of Toronto, Toronto, ON, Canada; Atlanta Cancer Care, Atlanta, GA; N. N. Blokhin Cancer Research Center, Russian Academy of Medical Sciences, Moscow, Russia; Roswell Park Cancer Institute, Buffalo, NY; Georgia Cancer Specialists, Georgia, GA; Southern Health, East Bentleigh, Australia; San Raffaele Scientific Institute, Milan, Italy; Vall d'Hebron University Hospital, Barcelona, Spain; START-Madrid, Centro Integral Oncológico Clara Campal, Madrid, Spain; Leuven Cancer Institute (LKI), Leuven, Belgium; Prince of Wales Hospital, Sydney, Australia; Celgene Corp, Summit, NJ; Bionomics Ltd., Thebarton, Australia; Celgene Corporation, Summit, NJ

Abstracts that were granted an exception in accordance with ASCO's Conflict of Interest Policy are designated with a caret symbol (^).

Abstract Disclosures

Abstract: 

Background: nab-Paclitaxel (nab-P, 130 nm albumin-bound paclitaxel) provides tumor selective localization via transcytosis across the endothelium, potential tumor uptake via macropinocytosis, and improved pharmacokinetics vs cremophor-paclitaxel. In vitro, nab-P increased tumoral gemcitabine (G) levels, and in a phase I/II study in metastatic pancreatic cancer (mPC) nab-P + G showed promising activity. Methods: Patients (pts) with mPC were randomized to nab-P 125 mg/m2, followed by G 1000 mg/m2 on days 1, 8, and 15 every 4 weeks or G 1000 mg/m2 weekly for 7 weeks (cycle 1), then on days 1, 8, and 15 every 4 weeks (≥ cycle 2). For the primary endpoint of overall survival (OS), 608 events from 842 patients provided a power of 0.9 to detect a HR of 0.769 (2-side α = 0.049). Results: 861 pts received therapy. Baseline pt characteristics were well balanced. Median age was 63 years, Karnofsky performance status was 90-100 in 60% and ≤80 in 40% of pts, 43% had head of pancreas lesions, 84% had liver and 39% had lung metastases, and 52% of pts had CA19-9 ≥59 x ULN. Treatment duration was 4 vs 3 months in nab-P + G vs G. The relative protocol G dose was 75% vs 85% in nab-P + G vs G; nab-P dose was 81%. OS, progression-free survival (PFS), time to treatment failure (TTF), and overall response rate (ORR) were significantly improved in the nab-P + G arm (Table). Most common grade ≥3 AEs were neutropenia (38% vs 27%), fatigue (17% vs 7%), and neuropathy (17% vs 1%) in the nab-P + G vs G arms. Grade ≥3 neuropathy improved to grade ≤1 in 29 days. Febrile neutropenia was reported in 3% (nab-P + G) vs 1% (G) pts. Conclusions: In this multinational, multiinstitutional study, nab-P + G was well tolerated and superior to G with statistically significant and clinically meaningful results in all endpoints and across subgroups. Clinical trial information: NCT00844649.

Intent-to-treat nab-P+G
n = 431
G
n = 430
Hazard ratio
(95%CI)
P =
OS, median mo 8.5 6.7 0.72 0.000015
 1-yr survival, % 35 22 (0.617–0.835) 0.000200
 2-yr survival, % 9 4 0.021234
PFS, median mo 5.5 3.7 0.69 0.000024
 1-yr PFS, % 16 9 (0.581–0.821) 0.031876
TTF, median mo 5.1 3.6 0.70
(0.604, 0.803)
<0.0001
Response rate ratio
(Pnab-P+G / PG)
ORR, n (%) 99 31 3.19 1.1x10-10
ORR, n (%) (23) (7) (2.178–4.662)