P-284 Phase 3 RECOURSE trial of TAS-102 versus placebo with best supportive care in patients with metastatic colorectal cancer: European subgroup

Abstract

Introduction: TAS-102 is comprised of an antineoplastic thymidine-based nucleoside analog, trifluridine, and the thymidine phosphorylase inhibitor, tipiracil hydrochloride, at a molar ratio of 1:0.5 (weight ratio, 1:0.471). The efficacy and safety of TAS-102 in patients with metastatic colorectal cancer refractory or intolerant to standard therapies were evaluated in the RECOURSE trial; enrollment criteria included ≥2 prior lines of standard chemotherapy (including prior fluoropyrimidine, oxaliplatin, irinotecan, bevacizumab, and an anti-EGFR antibody in patients with KRAS wild-type tumors). The primary results of RECOURSE demonstrated a significant improvement in overall survival and progression-free survival with TAS-102 versus placebo (hazard ratio [HR] = 0.68 and 0.48 for overall survival and progression-free survival, respectively; both P < 0.0001). The aim of this analysis is to evaluate efficacy and safety in the European subgroup of RECOURSE. Methods: This prespecified analysis of RECOURSE compared the efficacy and safety of TAS-102 versus placebo in European patients with metastatic colorectal cancer in the RECOURSE trial. The primary endpoint (overall survival) and key secondary efficacy endpoint (progression-free survival) were evaluated using univariate and multivariate analyses for the European subgroup. Results: The European subgroup (n = 403) consisted of 271 patients in the TAS-102 arm and 132 patients in the placebo arm. Both groups had a mean age of 62 years and 62% were male. The median overall survival in the European subpopulation was 6.8 months versus 4.9 months in the TAS-102 and placebo groups, respectively (HR = 0.62; 95% confidence interval [CI]: 0.48-0.80; P = 0.0002). Median progression-free survival was 2.0 months and 1.7 months in the TAS-102 and placebo groups, respectively (HR = 0.41; 95% CI: 0.33-0.52; P < 0.0001), and best overall response (complete response, partial response, or stable disease) was 42.1% of TAS-102 patients versus 12.5% of placebo patients. Overall adverse events and adverse events ≥ Grade 3 (Gr 3+) are shown in the Table. The most common Gr 3+ treatment-related adverse event was neutropenia (29.3% TAS-102 versus 0% placebo). Conclusion: As in the overall RECOURSE study group, TAS-102 was associated with significantly improved overall survival and progression-free survival compared with placebo. No new safety signals were seen in this European subpopulation of patients with metastatic colorectal cancer refractory to standard therapies. Table: P-284