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Eur J Cancer. 2018 Feb;90:63-72. doi: 10.1016/j.ejca.2017.10.009. Epub 2017 Dec 21.

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.

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University Hospital Gasthuisberg, Digestive Oncology, Herestraat 49, 3000 Leuven, Belgium; KU Leuven, Oude Markt 13, 3000 Leuven, Belgium. Electronic address:
Dana-Farber Cancer Institute, 450 Brookline Ave, Boston, MA 02215, USA. Electronic address:
University Hospital Ghent, De Pintelaan 185, 9000 Gent, Belgium. Electronic address:
Taiho Oncology, Inc., 101 Carnegie Center, Princeton, NJ 08540, USA. Electronic address:
Hospital Universitario 12 de Octubre, Avenida de Córdoba s/n, 28041 Madrid, Spain. Electronic address:
Hospital Regional Universitario de Málaga, Avenida de Carlos Haya s/n, 29011 Málaga, Spain. Electronic address:
Hospital Universitario Ramón y Cajal, Carretera de Colmenar Viejo, Km.9,100, 28034 Madrid, Spain. Electronic address:
CRLC Val d'Aurelle, 208 Avenue des Apothicaires, 34298 Montpellier, France. Electronic address:
Seconda Università degli Studi di Napoli, Via Antonio Vivaldi, 43, 81100 Caserta, Italy. Electronic address:
Università degli Studi di Milano, Via Festa del Perdono, 7, 20122 Milan, Italy; Niguarda Cancer Center, Grande Ospedale Metropolitano Niguarda, Piazza dell'Ospedale Maggiore, 3, 20162 Milan, Italy. Electronic address:
Cancer Institute Hospital of Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ward, Tokyo, 135-8550, Japan. Electronic address:
Aichi Cancer Center Hospital, 1-1 Kanokoden, Chikusa-ku, Nagoya, 464-8681, Japan. Electronic address:
Chiba Cancer Center, 666-2 Nitona-Cho, Chuo-ku, Chiba, 260-8717, Japan. Electronic address:
Tonan Hospital, N1 W6 Chuo-ku, Sapporo, Hokkaido, 060-0001, Japan. Electronic address:
Stathmi, Inc., 125 Brownsburg Rd, New Hope, PA 18938-9239, USA. Electronic address:
Indiana University Melvin and Bren Simon Cancer Center, 535 Barnhill Dr, Indianapolis, IN 46202, USA. Electronic address:
USC Norris Comprehensive Cancer Center, 1441 Eastlake Ave, Los Angeles, CA 90089, USA. Electronic address:
National Cancer Center Hospital East, 6-5-1 Kashiwanoha, Kashiwa, Chiba, 277-8577, Japan. Electronic address:



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 (<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.


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 NCT01607957.


Fluoropyrimidine; Metastatic colorectal cancer; Randomised controlled trial; TAS-102; Tipiracil; Trifluridine

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