VEGF Inhibitor Extends Survival

CHICAGO-Bevacizumab (Avastin) extends survival in advanced colorectal cancer by almost 5 months when added to standard chemotherapy, according to results from a major randomized trial. Herbert Hurwitz, MD, of Duke University Medical Center, lead investigator, presented these findings (ASCO abstract 3646). Bevacizumab(Drug information on bevacizumab) + IFL (bolus irinotecan [CPT-11, Camptosar], fluorouracil(Drug information on fluorouracil) [5-FU], and leucovorin) resulted in a median survival of 20.3 months compared to 15.6 months in the group receiving IFL + placebo, Dr. Hurwitz reported, extending survival by 4.4 months. Progression-free survival increased from 6.24 months to 10.6 months in the group receiving bevacizumab. The overall response rate rose from 34.7% in patients who received standard therapy plus placebo (n = 403), to 44.9% of patients given bolus IFL plus bevacizumab (n = 412), Dr. Hurwitz reported. Dr. Hurwitz said that bevacizumab was well tolerated and reported that grade 3/4 toxicity included bleeding (2.5% for the placebo arm vs 3.1% for the bevacizumab arm) and thromboembolism (16.1% vs 19.3%). Grade 3 hypertension increased from 2.3% in the placebo arm to 10.9% in the bevacizumab arm though Dr. Hurwitz said this was easily controlled with oral medication. Of greater concern, he noted, were six cases of gastrointestinal perforations that occurred in the bevacizumab arm, leading to death in one patient, and discontinuation of treatment in two patients. He cautioned that "an uncommon but serious complication of bevacizumab may have been identified." Bevacizumab is an antiangiogenesis agent that inhibits signaling from the vascular endothelial growth factor (VEGF), thereby cutting off the supply of blood to tumors. This was the first major trial to show the potential of an antiangiogenesis agent in treating human cancers.