%0 Journal Article
%A Van Cutsem, Eric
%A Mayer, Robert J
%A Laurent, Stéphanie
%A Winkler, Robert
%A Grávalos, Cristina
%A Benavides, Manuel
%A Longo-Munoz, Federico
%A Portales, Fabienne
%A Ciardiello, Fortunato
%A Siena, Salvatore
%A Yamaguchi, Kensei
%A Muro, Kei
%A Denda, Tadamichi
%A Tsuji, Yasushi
%A Makris, Lukas
%A Loehrer, Patrick
%A Lenz, Heinz-Josef
%A Ohtsu, Atsushi
%A RECOURSE Study Group
%T The subgroups of the phase III RECOURSE trial of trifluridine/tipiracil (TAS-102) versus placebo with best supportive care in patients with metastatic colorectal cancer.
%D 2017
%U http://hdl.handle.net/10668/11947
%X In the phase III RECOURSE trial, trifluridine/tipiracil (TAS-102) extended overall survival (OS) and progression-free survival (PFS) with an acceptable toxicity profile in patients with metastatic colorectal cancer refractory or intolerant to standard therapies. The present analysis investigated the efficacy and safety of trifluridine/tipiracil in RECOURSE subgroups. Primary and key secondary end-points were evaluated using a Cox proportional hazards model in prespecified subgroups, including geographical subregion (United States of America [USA], European Union [EU], Japan), age ( Eight-hundred patients were enrolled: USA, n = 99; EU, n = 403; Japan, n = 266. Patients aged ≥65 years and those with mutant KRAS tumours comprised 44% and 51% of all patients in the subregions, respectively. Final OS analysis (including 89% of events, compared with 72% in the initial analysis) confirmed the survival benefit associated with trifluridine/tipiracil, with a hazard ratio (HR) of 0.69 (95% confidence interval [CI] 0.59-0.81; P = 0.0001). Median OS in the three regions was 6.5-7.8 months in the trifluridine/tipiracil arm and 4.3-6.7 months in the placebo arm (USA: HR 0.56; 95% CI 0.34-0.94; P = 0.0277; EU: HR 0.62; 95% CI 0.48-0.80; P = 0.0002; Japan: HR 0.75; 95% CI 0.57-1.00; P = 0.0470). Median PFS was 2.0-2.8 months for trifluridine/tipiracil and 1.7-1.8 months for placebo; HRs favoured trifluridine/tipiracil in all regions. Similar clinical benefits of trifluridine/tipiracil were observed in elderly patients and in those with mutant KRAS tumours. There were no marked differences among subregions in terms of safety and tolerability. Trifluridine/tipiracil was effective in all subgroups, regardless of age, geographical origin or KRAS status. This trial is registered with ClinicalTrials.gov: NCT01607957.
%K Fluoropyrimidine
%K Metastatic colorectal cancer
%K Randomised controlled trial
%K TAS-102
%K Tipiracil
%K Trifluridine
%~