Phase III RECOURSE trial of TAS-102 versus placebo with best supportive care in patients with metastatic colorectal cancer: Geographic subgroups.

Abstract

646 Background: 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 (pts) with metastatic colorectal cancer refractory/intolerant to standard therapies were evaluated in the RECOURSE trial; enrollment criteria included ≥ 2 prior lines of standard chemotherapy. Primary results of RECOURSE demonstrated a significant improvement in overall survival (OS) and progression-free survival (PFS) with TAS-102 vs placebo (PBO) (hazard ratio [HR] = 0.68 and 0.48 for OS and PFS, respectively; both P< 0.0001). Methods: RECOURSE data were evaluated for efficacy and safety, including rate of hospitalizations, of TAS-102 vs PBO by each geographic subgroup of US, EU, and Japan (JP). Results: Of 768 pts, 99 US (mean age, 60 y), 403 EU (mean age, 62 y), and 266 JP (mean age, 62 y) pts were randomized to receive TAS-102 or PBO. Median OS with TAS-102 vs PBO was 6.5 mo vs 4.3 mo in US pts, 6.8 mo vs 4.9 mo in EU pts, and 7.8 mo vs 6.7 mo in JP pts. HRs for OS and PFS for US, EU, and JP pts all favored TAS-102 (Table). There were no marked differences among the US, EU, and JP subgroups with respect to overall incidence of adverse events (AEs), ≥ Grade 3 AEs, serious AEs (SAEs), or hospitalizations. Conclusions: Similar to the overall RECOURSE population, OS and PFS benefits were observed in each geographic subgroup randomized to TAS-102 vs PBO, with an acceptable safety profile. Clinical trial information: NCT01607957. [Table: see text] [Table: see text]