Adding Bevacizumab to 5-FU/LV Reduced Risk of Death by 25%

SOUTH SAN FRANCISCO- Adding bevacizumab(Drug information on bevacizumab) (Avastin) to 5-FU/leucovorin (LV) reduced risk of death by 25% vs 5-FU/LV or irinotecan(Drug information on irinotecan) (CPT-11, Camptosar)/5-FU/LV (IFL), according to a retrospective combined analysis. "We showed a quite significant survival in the group when we add bevacizumab to 5-FU/LV," said investigator Robert D. Mass, MD, director of Oncology, Genentech, Inc., South San Francisco, California. The investigators cited several studies showing that bevacizumab improved survival time in metastatic colorectal cancer. These include a phase III randomized trial (N Engl J Med 350(23):2335-2342, 2004) using bevacizumab and IFL, and three randomized studies in which bevacizumab was combined with 5-FU/LV. "The difficulty with all of these studies is that they were all quite small, and they all had very strong trends in survival, but none of them reached statistical significance," Dr. Mass said. To address this issue, Genentech investigators performed a combined analysis, in which data for bevacizumab/ 5-FU/LV-treated patients was pooled and compared with a "combined control" of 5-FU/LV and IFL (abstract 3616). "It was basically a method by which we could get more robust statistics," Dr. Mass said at the 40th Annual Meeting of the American Society of Clinical Oncology. The combined analysis included a total of 249 patients who received bevacizumab/ 5-FU/LV (with the bevacizumab 5-mg dose) and 241 receiving either 5-FU/LV alone or IFL. All the studies used the standard Roswell Park bolus 5-FU/LV regimen. Dr. Mass reported a 25% reduction in risk of death for patients receiving the bevacizumab-containing regimen vs 5-FU/LV or IFL alone (hazard ratio [HR] = 0.742, 95% confidence interval, 0.59-0.93). Overall survival time was 17.9 months, vs 14.6 months in the combined control group (P = .0081). "The survival numbers were not quite significant for any of these trials by themselves," Dr. Mass said, "but when we looked at them as a combined analysis, we saw a highly significant [difference]." Progression-free survival time was significantly increased in the bevacizumab/ 5-FU/LV group, from 5.6 months to 8.8 months (HR = 0.63, P = .0001). Interpretation of safety differences was confounded by inclusion of IFL-treated patients in the control group, although adverse events were "consistent" with what was reported in the individual trials, according to investigators. Wide Survival Benefits In a related study, Genentech investigators described a subgroup analysis of survival from the phase III trial of bevacizumab/IFL recently reported in the New England Journal of Medi-cine. Investigators reported an increase in survival from 15.6 months for IFL to 20.3 months for bevacizumab/IFL (P < .001). To evaluate the effects of baseline risk factors on survival, they analyzed a number of risk factors, including performance status, primary tumor site, age, sex, race, prior treatment, and duration of metastatic disease, as well as baseline levels of albumin, alkaline phosphatase, and lactate dehydrogenase. The survival benefit, however, was seen in all these prespecified subgroups. For example, median survival time increased from 14.9 months to 21.6 months for patients who had received prior radiotherapy, and from 15.6 months to 19.9 months for those who had not. Adjusting for a number of baseline factors, investigators determined that the addition of bevacizumab resulted in a 34% reduction in hazard of death vs those patients who had received placebo. "It didn't matter whether [patients] were old or young, had low or high albumins, or poor vs good performance status," Dr. Mass said. "Bevacizumab plus IFL benefited all the prespecified subsets."