AVASTIN IN GASTRIC CANCER-ANOTHER FAILURE

J Clin Oncol. 2011 Aug 15. [Epub ahead of print]

Bevacizumab in Combination With Chemotherapy As First-Line Therapy in Advanced Gastric Cancer: A Randomized, Double-Blind, Placebo-Controlled Phase III Study.

Ohtsu A, Shah MA, Van Cutsem E, Rha SY, Sawaki A, Park SR, Lim HY, Yamada Y, Wu J, Langer B, Starnawski M, Kang YK

Abstract

PURPOSE The Avastin in Gastric Cancer (AVAGAST) trial was a multinational, randomized, placebo-controlled trial designed to evaluate the efficacy of adding bevacizumab to capecitabine-cisplatin in the first-line treatment of advanced gastric cancer. PATIENTS AND METHODS Patients received bevacizumab 7.5 mg/kg or placebo followed by cisplatin 80 mg/m(2) on day 1 plus capecitabine 1,000 mg/m(2) twice daily for 14 days every 3 weeks. Fluorouracil was permitted in patients unable to take oral medications. Cisplatin was given for six cycles; capecitabine and bevacizumab were administered until disease progression or unacceptable toxicity. The primary end point was overall survival (OS). Log-rank test was used to test the OS difference. Results In all, 774 patients were enrolled; 387 were assigned to each treatment group (intention-to-treat population), and 517 deaths were observed. Median OS was 12.1 months with bevacizumab plus fluoropyrimidine-cisplatin and 10.1 months with placebo plus fluoropyrimidine-cisplatin (hazard ratio 0.87; 95% CI, 0.73 to 1.03; P = .1002). Both median progression-free survival (6.7 v 5.3 months; hazard ratio, 0.80; 95% CI, 0.68 to 0.93; P = .0037) and overall response rate (46.0% v 37.4%; P = .0315) were significantly improved with bevacizumab versus placebo. Preplanned subgroup analyses revealed regional differences in efficacy outcomes. The most common grade 3 to 5 adverse events were neutropenia (35%, bevacizumab plus fluoropyrimidine-cisplatin; 37%, placebo plus fluoropyrimidine-cisplatin), anemia (10% v 14%), and decreased appetite (8% v 11%). No new bevacizumab-related safety signals were identified. CONCLUSION Although AVAGAST did not reach its primary objective, adding bevacizumab to chemotherapy was associated with significant increases in progression-free survival and overall response rate in the first-line treatment of advanced gastric cancer.