Bevacizumab Combined with S-1 and Raltitrexed for Patients with Metastatic Colorectal Cancer Refractory to Standard Therapies: A Phase II Study.

Lessons learned Bevacizumab combined with S-1 and raltitrexed demonstrated positive anti-tumor efficacy and acceptable toxicity. This combination might represent a treatment option for refractory metastatic colorectal cancer. Background In patients with metastatic colorectal cancer (mCRC) refractory to standard therapies, S-1 plus raltitrexed showed a good objective response rate (ORR) and significant survival benefit in our previous study. In the present study, we assessed the activity and safety of bevacizumab combined with S-1 and raltitrexed. Methods This investigator-initiated, open-label, single-arm, phase II trial was performed at West China Hospital in China. Patients with mCRC who had disease progression after fluoropyrimidine, irinotecan, and oxaliplatin and had at least one measurable lesion, were eligible for this trial. Anti-EGFR therapy (for tumors with wild-type RAS) and anti-VEGF in first- or second-line was allowed, but patients who had been treated with bevacizumab across two consecutive chemotherapy regimens were excluded. Patients received bevacizumab (7.5 mg/kg on day1), oral S-1 (80-120 mg per day for 14 days), and raltitrexed (3 mg/m2 on day 1), every 3 weeks. The primary endpoint was ORR. Secondary endpoints included progression-free survival (PFS), overall survival (OS), and toxicity. Results From Sep 2015 to Nov 2019, 44 patients were enrolled. Tumor response evaluation was available in 44 patients at the time of the analysis. There were no complete responses; the ORR was 15.9%, and disease control rate was 54.5%. Median PFS and OS were 110 days (95% confidence interval [CI], 65.0-155.0) and 367 days (95% CI, 310.4-423.6), respectively. The combination was well tolerated. Conclusion Bevacizumab combined with S-1 and raltitrexed showed promising anti-tumor activity and safety in refractory mCRC.