Van Cutsem, EricMayer, Robert JLaurent, StéphanieWinkler, RobertGrávalos, CristinaBenavides, ManuelLongo-Munoz, FedericoPortales, FabienneCiardiello, FortunatoSiena, SalvatoreYamaguchi, KenseiMuro, KeiDenda, TadamichiTsuji, YasushiMakris, LukasLoehrer, PatrickLenz, Heinz-JosefOhtsu, AtsushiRECOURSE Study Group2023-01-252023-01-252017-12-21http://hdl.handle.net/10668/11947In 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.enAttribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/FluoropyrimidineMetastatic colorectal cancerRandomised controlled trialTAS-102TipiracilTrifluridineAdultAgedAntineoplastic Combined Chemotherapy ProtocolsColorectal NeoplasmsDisease-Free SurvivalDouble-Blind MethodDrug CombinationsFemaleHumansKaplan-Meier EstimateMaleMiddle AgedProportional Hazards ModelsPyrrolidinesThymineTreatment OutcomeTrifluridineUracilresearch article29274618open access10.1016/j.ejca.2017.10.0091879-0852PMC7493695http://www.ejcancer.com/article/S0959804917313497/pdfhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7493695/pdf