SALTO is a multi-center, open-label phase III trial in which 161 Western patients with metastatic colorectal cancer (mCRC) were randomized between capecitabine and S-1. The primary endpoint, a lower incidence of hand-foot syndrome (HFS) for S-1, was met (all grade 73% for capecitabine versus 45% for S-1, odds ratio 0.31 [95% confidence interval (CI) 0.16-0.60], p = 0.0005; grade 3 21% for capecitabine versus 4% for S-1, p = 0.003). There was no significant difference in median progression-free survival (PFS), data on overall survival (OS) were immature. We here present updated results on survival.
mCRC patients in whom first-line fluoropyrimidine monochemotherapy was indicated were randomized between capecitabine twice-daily on day 1 to 14 at a dose of 1250 mg/m2 for patients <70 years or 1000 mg/m2 for patients ≥70 years of age, or S-1 twice-daily on day 1 to 14 at a dose of 30 mg/m2, irrespective of age. Co-treatment with bevacizumab, 7.5 mg/kg intravenously on day 1, was optional. Cycles were repeated every 3 weeks. The primary endpoint was the incidence of HFS, secondary endpoints included PFS and OS.
A total of 161 patients were randomized between January 2014 - July 2015, 81 in the capecitabine group and 80 in the S-1 group. Bevacizumab was administered to 59% of patients in both arms. At data cut-off (6 August 2018, median follow-up 40.3 months), 71 (88%) patients in the capecitabine group and 68 (85%) patients in the S-1 group had died. Median PFS was 8.2 months (95% CI 6.4-10.3) for capecitabine and 8.4 months (95% CI 6.4-10.6) for S-1 (HR 1.02, 95% CI 0.75-1.40, p = 0.89). Median OS was 17.1 months (95% CI 14.3-23.5) and 17.0 months (13.0-20.1), respectively (HR 1.07, 95% CI 0.76-1.49, p = 0.70).
This study demonstrated a significantly lower incidence of HFS for S-1 compared to capecitabine in Western mCRC patients. Although the study was not powered to demonstrate non-inferiority, these data suggest comparable efficacy of S-1 and capecitabine in terms of PFS and OS.
Clinical trial identification
Legal entity responsible for the study
Dutch Colorectal Cancer Group.
J.J. Kwakman: Honoraria (self), Research grant / Funding (institution): Nordic Pharma; Advisory / Consultancy, Research grant / Funding (institution): Servier. R. van Alphen: Advisory / Consultancy: Nordic Pharma; Travel / Accommodation / Expenses: Roche. C.J.A. Punt: Advisory / Consultancy: Nordic Pharma; Advisory / Consultancy: Servier. All other authors have declared no conflicts of interest.