Making Independence Work: Monitoring the Bevacizumab Colorectal Cancer Clinical Trial

Abstract

Genentech’s phase III study of colorectal cancer aimed to show that administration of bevacizumab, its recombinant human anti-vascular endothelial growth factor antibody, to patients with metastatic colorectal cancer would reduce mortality. The four-member DMC was responsible for reviewing real-time safety data, selecting the experimental arm of the study at an interim analysis, and assessing efficacy at a second interim analysis. Genentech and the entire study team remained blinded to treatment allocation during the course of the trial. The study, which proceeded to its planned end, showed an estimated hazard ratio for death of 0.66 (p < 0.001). On the basis of this study, the FDA approved bevacizumab for patients with metastatic colon cancer. This example shows how a DMC can make complicated decisions and recommendations even when neither it nor the statisticians reporting to it participate in any other way with the conduct of the study.