Updated results of the SOFT study: A randomized phase III trial of S-1/oxaliplatin (SOX) plus bevacizumab versus 5-FU/l-LV/oxaliplatin (mFOLFOX6) plus bevacizumab in patients with metastatic colorectal cancer (mCRC).

3586 Background: As previously reported (Yamada Y, et al. Lancet Oncol. 2013 Dec;14(13):1278-86), the SOFT study demonstrated that SOX plus bevacizumab (SOX+Bev) was non-inferior to mFOLFOX6 plus bevacizumab (mFOLFOX6+Bev) in terms of the primary endpoint of progression-free survival (PFS). We now report the final overall survival (OS) after a median follow-up of more than 3 years. Methods: The SOFT study was an open-label, non-inferiority, randomized phase III trial. Chemotherapy-naïve patients with mCRC, an ECOG PS of 0-1, and adequate organ functions were randomized to receive either mFOLFOX6+Bev (5 mg/kg of bevacizumab, followed by 200 mg/m2 of l-leucovorin given simultaneously with 85 mg/m2 of oxaliplatin, followed by a 400 mg/m2 bolus of 5-FU on day 1 and then 2,400 mg/m2 of 5-FU as an intravenous infusion over the course of 46 h, every 2 weeks) or SOX+Bev (7.5 mg/kg of bevacizumab, 130 mg/m2 of oxaliplatin on day 1, and 40−60 mg of S-1 twice daily for 2 weeks, followed by a 1-week rest). The primary endpoint was PFS. Patients’ data were finally updated in September 2013. Results: At this final analysis, the median survival time(MST) was 29.7 months (95% CI: 26.5−33.1) with mFOLFOX6+Bev and 29.6 months (95% CI: 25.8−34.7) with SOX+Bev (median follow-up, 37.7 months). The HR for OS was 1.018 (95% CI: 0.823−1.258). Median PFS was 11.7 months (95% CI: 10.9−13.3) with mFOLFOX6+Bev and 12.2 months (95% CI: 10.7−13.0) with SOX+Bev. The HR for PFS was 1.051 (95% CI: 0.876−1.262), and the p value for non-inferiority was 0.0115 (median follow-up, 31.2 months). In the subgroup analysis of PFS and OS, we recorded no clinically significant interactions between the assigned regimen and any factors. The safety profile was almost similar to primary analysis results. Conclusions: In this study, the MST was at least 29.5 months in both groups, indicating similar OS. Our results reconfirmed that SOX+Bev is non-inferior to mFOLFOX6+Bev in terms of PFS as first-line treatment for mCRC. SOX+Bev can thus be used instead of mFOLFOX6+Bev. Clinical trial information: JapicCTI-090699.