Bevacizumab (a monoclonal antibody to vascular endothelial growth factor) to prolong progression-free survival in first-line colorectal cancer (CRC) in subjects who are not suitable candidates for first-line CPT-11

Abstract

3516 Background: Bevacizumab [Avastin (BV)] is a recombinant, humanized monoclonal antibody directed against vascular endothelial growth factor. As presented at ASCO 2003, the addition of BV to IFL chemotherapy prolonged median survival from 15.61 months to 20.34 months (p = 0.00004). This was a companion trial that studied the addition of BV to FU/LV chemotherapy in subjects who were not optimal candidates for first-line irinotecan because of age or performance status. Methods: Approximately 200 patients were to be randomized to receive the Roswell Park regimen of FU/LV placebo or FU/LV/BV (5 mg/kg every two weeks). The primary efficacy endpoint was survival; secondary efficacy endpoints included progression free survival (PFS), objective response rate (ORR) and duration of response. Results: 209 patients were randomized between September 7, 2000 and May 6, 2002. For the two groups, FU/LV/Placebo and FU/LV/BV, baseline characteristics were similar. Efficacy and selected safety results are as follows: Conclusions: The addition of BV to FU/LV chemotherapy, in subjects who are not optimal candidates for first-line CPT-11 resulted in a clinically meaningful and statistically significant prolongation of progression-free survival and trends towards improved response rate,duration of response, and survival as compared with FU/LV chemotherapy alone. The addition of BV to FU/LV was well tolerated; Grade 3 hypertension, easily managed with oral medications was increased with BV, The uncommon but life-threatening event of gastrointestinal perforation occurred in 2 patients in the FU/LV/BV arm Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Genentech, Inc. Genentech, Inc. Genentech, Inc. Genentech, Inc.