Efficacy and safety of bevacizumab plus chemotherapy in chinese patients with metastatic colorectal cancer:A randomized phase iii artist trial

Abstract

The efficacy and safety of bevacizum ab with modified irinotecan, leucovorin bolus, and 5-fl uorouracil intravenous infusion (mIFL) in the first-lin e treatment of metastatic colorectal cancer (mCRC) has not been well evaluated in randomized clinical trials in Chinese patients. We conducted a phrase III trial in which patients with previously untreated mCRC were randomized 2:1 to the mIFL[irinotecan(125 mg/m2), leucovorin(20 mg/m2) bolus, and 5-fl uorouracil intravenous infusion(500 mg/m2) weekly for four weeks every six weeks] plus bevacizumab (5 mg/kg every two weeks) group and the mIFL group, respectively. Co-primary objectives were progression-free survival (PFS) and 6-m onth PFS rate. In total, 214 patients were enrolled. Our results showed that addition of bevacizumab to mIFL significantly improved median PFS (4.2 months in the mIFL group vs. 8.3 months in the bevacizumab plus mIFL group, P < 0.001), 6-m onth PFS rate (25.0% vs. 62.6%, P < 0.001), median overall survival (13.4 months vs. 18.7 months, P = 0.014), and response rate (17% vs. 35%, P = 0.013). Grades 3 and 4 adverse events included diarrhea (21% in the mIFL group and 26% in the bevacizumab plus mIFL group) and neutropenia (19% in the mIFL group and 33% in the bevacizumab plus mIFL group). No wound-h ealing complications or congestive heart failure occurred. Our results suggested that bevacizumab plus mIFL is effective and well tolerated as first- line treatment for Chinese patients with mCRC. Clinical benefit and safety profiles were consistent with those observed in pivotal phase III trials with mainly Caucasian patients.