S-1 and irinotecan plus bevacizumab versus mFOLFOX6 or CapeOX plus bevacizumab as first-line treatment in patients with metastatic colorectal cancer (TRICOLORE): a randomized, open-label, phase 3, non-inferiority trial

Abstract

Background

Combination therapy with oral fluoropyrimidine and irinotecan has not yet been established as first-line treatment for metastatic colorectal cancer (mCRC). We performed a randomized, open-label, phase 3 trial to determine whether S-1 and irinotecan plus bevacizumab is non-inferior to mFOLFOX6 or CapeOX plus bevacizumab in terms of progression-free survival (PFS).

Patients and methods

Patients from 53 institutions who had previously untreated mCRC were randomly assigned (1:1) to receive either mFOLFOX6 or CapeOX plus bevacizumab (control group) or S-1 and irinotecan plus bevacizumab (experimental group; a 3-week regimen: intravenous infusions of irinotecan 150 mg/m² and bevacizumab 7.5 mg/kg on day 1, oral S-1 80 mg/m² twice daily for 2 weeks, followed by a 1-week rest; or a 4-week regimen: irinotecan 100 mg/m² and bevacizumab 5 mg/kg on days 1 and 15, S-1 80 mg/m² twice daily for 2 weeks, followed by a 2-week rest). The primary endpoint was PFS. The non-inferiority margin was 1.25; non-inferiority would be established if the upper limit of the 95% CI for the hazard ratio (HR) of the control versus the experimental group was less than this margin.

Results

Between June 2012 and September 2014, 487 patients underwent randomization. 243 patients assigned to the control group and 241 assigned to the experimental group were included in the primary analysis. Median PFS was 10.8 months (95% CI 9.6 − 11.6) in the control group and 14.0 months (95% CI 12.4 − 15.5) in the experimental group (HR 0.84, 95% CI 0.70 − 1.02; P<0.0001 for non-inferiority, P=0.0815 for superiority). 157 patients (64.9%) in the control group and 140 (58.6%) in the experimental group had adverse events of grade 3 or higher.

Conclusion

S-1 and irinotecan plus bevacizumab is non-inferior to mFOLFOX6 or CapeOX plus bevacizumab with respect to PFS as first-line treatment for mCRC and could be a new standard treatment.

Clinical trials number

UMIN000007834