(ChemotherapyAdvisor) – Weekly nanoparticle albumin-bound (nab)-paclitaxel plus gemcitabine significantly improved survival in patients with metastatic adenocarcinoma of the pancreas compared with gemcitabine alone, results of a global phase 3 trial reported in advance of being presented during the 10th annual Gastrointestinal Cancers Symposium on January 25th in San Francisco, CA.
“In this study, nab-paclitaxel plus gemcitabine was well tolerated and superior to gemcitabine with statistically significant and clinically meaningful results in all end points and across subgroups,” stated Daniel D. Von Hoff, MD, of the Virginia G. Piper Cancer Center at Scottsdale Healthcare/Translational Genomics Research Institute (TGen), Scottsdale, AZ, on behalf of the study investigators.
The Metastatic Pancreatic Adenocarcinoma Clinical Trial (MPACT) randomly assigned 861 patients to nab-paclitaxel 125 mg/m2 followed by gemcitabine 1,000 mg/m2 on days 1, 8, and 15 every 4 weeks (n=431) or gemcitabine 1,000 mg/m2 weekly alone for 7 weeks (cycle 1), then days 1, 8, and 15 every 4 weeks in subsequent cycles (n=430).
Baseline characteristics were well balanced between the two arms. Median age was 63 years and Karnofsky performance status was 90-100 in 60% of patients. Head of pancreas lesions were present in 43% of patients; 84% had metastases of the liver and 39%, the lung; and 52% had CA 19-9 ≥59 x ULN (upper limit of normal). Treatment duration was 4 months in the nab-paclitaxel/gemcitabine arm and 3 months in the gemcitabine-alone arm.
In the nab-paclitaxel/gemcitabine arm, median overall survival (OS) was 8.5 months versus 6.7 months in the gemcitabine alone arm (hazard ratio [HR], 0.72; 95% CI: 0.617–0.835; P=0.000015). One-year survival was 35% and 22% (P=0.0002) and 2-year survival, 9% and 4% (P=0.02), respectively.
Median progression-free survival (PFS) was 5.5 months in the nab-paclitaxel/gemcitabine arm and 3.7 months in the gemcitabine-alone arm (HR, 0.69; 95% CI: 0.581–0.821; P=0.000024) and 1-year PFS was 16% and 9% (P=0.031876).
Median time to treatment failure was 5.1 months in the combination arm and 3.6 months in the gemcitabine arm (HR, 0.70; 95% CI: 0.604–0.803; P<0.0001).
Overall response rate was 23% for nab-paclitaxel/gemcitabine compared with 7% for gemcitabine alone (response rate ratio 3.19; P=1.1 x 10-10).
The most common grade ≥3 adverse events were neutropenia (38% in the nab-paclitaxel plus gemcitabine arm vs. 27% in the gemcitabine arm), fatigue (17% vs. 7%), and neuropathy (17% vs. 1%). Grade ≥3 neuropathy improved to grade ≤1 in 29 days, Dr. Von Hoff reported. Febrile neutropenia was reported in 3% of patients in the combination arm versus 1% in the gemcitabine arm.
The 2013 Gastrointestinal Cancers Symposium is co-sponsored by the American Gastroenterological Association (AGA) Institute, the American Society of Clinical Oncology (ASCO), the American Society for Radiation Oncology (ASTRO), and the Society of Surgical Oncology (SSO).