Cutsem, Eric VanMayer, Robert J.Laurent, StéphanieWinkler, RobertGrávalos, CristinaBenavides, ManuelLongo-Munoz, FedericoPortales, FabienneCiardiello, FortunatoSiena, SalvatoreYamaguchi, KenseiMuro, KeiDenda, TadamichiTsuji, YasushiMakris, LukasLoehrer, PatrickLenz, Heinz-JosefOhtsu, Atsushi2021-05-052021-05-052017-12-01Cutsem, E. V., Mayer, R. J., Laurent, S., Winkler, R., Grávalos, C., Benavides, M., Longo-Munoz, F., Portales, F., Ciardiello, F., Siena, S., Yamaguchi, K., Muro, K., Denda, T., Tsuji, Y., Makris, L., Loehrer, P., Lenz, H.-J., & Ohtsu, A. (2018). 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. European Journal of Cancer, 90, 63–72. https://doi.org/10.1016/j.ejca.2017.10.0090959-8049, 1879-0852https://hdl.handle.net/1805/25886Background: 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. Methods: 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 (<65 years, ≥65 years) and v-Ki-ras2 Kirsten rat sarcoma 2 viral oncogene homologue (KRAS) status (wild type, mutant). Safety and tolerability were reported with descriptive statistics. Results: 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. Conclusions: Trifluridine/tipiracil was effective in all subgroups, regardless of age, geographical origin or KRAS status.en-USFluoropyrimidineMetastatic colorectal cancerRandomised controlled trialTAS-102TipiracilTrifluridineArticle