Gemcitabine Plus Bevacizumab Compared With Gemcitabine Plus Placebo in Patients With Advanced Pancreatic Cancer: Phase III Trial of the Cancer and Leukemia Group B (CALGB 80303)

作者：Hedy Lee Kindler, Donna Niedzwiecki, Donna R. Hollis, Susan Sutherland, Deborah Schrag, Herbert I. Hurwitz, Federico Innocenti, Mary F. Mulcahy, Eileen Mary O'Reilly, Timothy F. Wozniak, Joel Picus, Pankaj Bhargava, Robert J. Mayer, Richard L. Schilsky, Richard M. Goldberg · 发表于：Journal of Clinical Oncology · 年份：2010 · DOI：10.1200/jco.2010.28.1386 · 被引用次数：853 · 研究领域：Pancreatic and Hepatic Oncology Research、Pancreatitis Pathology and Treatment、Cholangiocarcinoma and Gallbladder Cancer Studies

PURPOSE: The combination of gemcitabine plus bevacizumab produced a 21% response rate and a median survival of 8.8 months in a multicenter phase II trial in patients with metastatic pancreatic cancer. These encouraging data led Cancer and Leukemia Group B (CALGB) to conduct a double-blind, placebo-controlled, randomized phase III trial of gemcitabine/bevacizumab versus gemcitabine/placebo in advanced pancreatic cancer patients. PATIENTS AND METHODS: Eligible patients had no prior therapy for advanced disease, Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2, no tumor invasion of adjacent organs, and no increased bleeding risk. The primary end point was overall survival. Patients were stratified by performance status, extent of disease, and prior radiotherapy. Patients received gemcitabine at 1,000 mg/m(2) over 30 minutes on days 1, 8, and 15 every 28 days and bevacizumab at 10 mg/kg or placebo on days 1 and 15 every 28 days. RESULTS: Between June 2004 and April 2006, 602 patients were enrolled onto the study and 535 were treated. Median overall survival was 5.8 months for gemcitabine/bevacizumab and 5.9 months for gemcitabine/placebo (P = .95). Median progression-free survival was 3.8 and 2.9 months, respectively (P = .07). Overall response rates were 13% and 10%, respectively. Patients with a performance status of 0, 1, and 2 survived a median of 7.9, 4.8, and 2.4 months, respectively. The only statistically significant differences in grades 3 and 4 toxici...