The clinical benefit of bevacizumab in metastatic colorectal cancer is independent of K-ras mutation status: analysis of a phase III study of bevacizumab with chemotherapy in previously untreated metastatic colorectal cancer.

Purpose. Mutations of the K-ras gene were identified as a prognostic marker in metastatic colorectal cancer (mCRC). In addition, emerging data suggest that K-ras mutations are a negative predictor of clinical benefit from anti–epidermal growth factor receptor treatment in mCRC. Previously reported data suggest that the longer overall survival (OS) observed with bevacizumab treatment in mCRC is independent of alterations in the Ras/ Raf/Mek/Erk pathway. We conducted additional analyses tobetterdescribetheclinicalbenefitofbevacizumabtreatment in mCRC relative to K-ras mutation status. Patients and Methods. Additional statistical analyses were done with data from K-ras mutation analyses in 230 patients who were treated with irinotecan, fluorouracil, and leucovorin (IFL) in combination with either bevacizumab or placebo in a randomized phase III study. Following microdissection, tissue was subject to DNA sequencing to identify K-ras mutations in codons 12and13.Hazardratiosforthebevacizumabgrouprelative to the control group were estimated from an unstratified Cox regression model. The median progression-freesurvival(PFS),OStimes,andobjectiveresponse rates were compared. Results. K-ras status was assessed in 230 patients (28.3%).ThemedianPFSwassignificantlylongerinbevacizumab-treated patients with wild-type (wt)- (13.5 versus 7.4 months; hazard ratio 0.44, p < .0001) and mutant (m)-K-ras (9.3 versus 5.5 months; hazard ratio