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

Date 04 July 2015
Event WorldGI 2015
Session Posters
Topics Anti-Cancer Agents & Biologic Therapy
Supportive Care
Colon Cancer
Rectal Cancer
Presenter A. Falcone
Citation Annals of Oncology (2015) 26 (suppl_4): 1-100. 10.1093/annonc/mdv233
Authors A. Falcone1, A. Ohtsu2, F. Ciardiello3, E. Van Cutsem4, F. Longo Munoz5, M. Ychou6, K. Muro7, Y. Tsuji8, M. Benavides9, S. Laurent10, C. Grávalos11, S. Siena12, K. Yamaguchi13, T. Denda14, N. Tebbutt15, P.J. Loehrer16, H.-. Lenz17, R.J. Mayer18
  • 1University of Pisa, Pisa/IT
  • 2National Cancer Center, Kashiwashi/JP
  • 3Seconda Universita Degli Studi Di Napoli, Naples/IT
  • 4Leuven Cancer Institute, University Hospitals Leuven, Leuven/
  • 5Ramón y Cajal University Hospital, Madrid/ES
  • 6Institut Régional du Cancer de Montpellier, Montpellier/FR
  • 7Aichi Cancer Center Hospital, Nagoya/JP
  • 8Tonan Hospital, Sapporo/JP
  • 9Hospital Regional Universitario Carlos Haya, Málaga/ES
  • 10University Hospital Ghent, Ghent/BE
  • 11Hospital Universitario 12 de Octubre, Madrid/ES
  • 12Ospedale Niguarda Ca' Granda, Milano/IT
  • 13Saitama Cancer Center, Inamachi/JP
  • 14Chiba Cancer Center, Chiba/JP
  • 15Austin Hospital, Melbourne/AU
  • 16Indiana University Simon Cancer Center, Indianapolis/US
  • 17University of Southern California Norris Comprehensive Cancer Center, Los Angeles/US
  • 18Dana-Farber Cancer Institute, Boston/US

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