Modest DP, et al. - In the XELAVIRI trial, two treatment approaches for untreated metastatic colorectal cancer were tested. Whether initial treatment with a fluoropyrimidine plus bevacizumab, followed by the addition of irinotecan at first progression (arm A) was noninferior to upfront use of fluoropyrimidine plus irinotecan plus bevacizumab (arm B) was investigated in a 1:1 randomized, controlled phase III trial. The full analysis set comprised 421 randomly assigned patients (arm A: n = 212; arm B: n = 209), with 71 and 69 years as respective median age. For time to failure of the strategy (TFS, primary efficacy end point), noninferiority of sequential escalation therapy vs initial combination chemotherapy could not be shown. For RAS/BRAF wild-type tumors, an obviously superior therapy was upfront combination therapy, whereas comparable results with sequential escalation chemotherapy were noted in patients with RAS mutant tumors. This finding suggests the possible importance of RAS status as a guide to therapy.