VEGF Inhibitor Extends Survival

CHICAGO-Bevacizumab(Avastin) extends survival in advancedcolorectal cancer by almost 5 monthswhen added to standard chemotherapy,according to results from a majorrandomized trial. Herbert Hurwitz,MD, of Duke University Medical Center,lead investigator, presented thesefindings (ASCO abstract 3646).Bevacizumab + IFL (bolus irinotecan[CPT-11, Camptosar], fluorouracil[5-FU], and leucovorin) resultedin a median survival of 20.3 monthscompared to 15.6 months in the groupreceiving IFL + placebo, Dr. Hurwitzreported, extending survival by 4.4months. Progression-free survival increasedfrom 6.24 months to 10.6months in the group receiving bevacizumab.The overall response rate rose from34.7% in patients who received standardtherapy plus placebo (n = 403),to 44.9% of patients given bolus IFLplus bevacizumab (n = 412), Dr. Hurwitzreported.Dr. Hurwitz said that bevacizumabwas well tolerated and reportedthat 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%). Grade3 hypertension increased from 2.3%in the placebo arm to 10.9% in thebevacizumab arm though Dr. Hurwitzsaid this was easily controlledwith oral medication.Of greater concern, he noted, weresix cases of gastrointestinal perforationsthat occurred in the bevacizumabarm, leading to death in one patient,and discontinuation of treatmentin two patients. He cautioned that"an uncommon but serious complicationof bevacizumab may have beenidentified."Bevacizumab is an antiangiogenesisagent that inhibits signaling fromthe vascular endothelial growth factor(VEGF), thereby cutting off the supplyof blood to tumors. This was thefirst major trial to show the potentialof an antiangiogenesis agent in treatinghuman cancers.