PMID- 27443414 OWN - NLM STAT- MEDLINE DCOM- 20170214 LR - 20201209 IS - 1699-3055 (Electronic) IS - 1699-048X (Print) IS - 1699-048X (Linking) VI - 19 IP - 2 DP - 2017 Feb TI - Efficacy of trifluridine and tipiracil (TAS-102) versus placebo, with supportive care, in a randomized, controlled trial of patients with metastatic colorectal cancer from Spain: results of a subgroup analysis of the phase 3 RECOURSE trial. PG - 227-235 LID - 10.1007/s12094-016-1528-7 [doi] AB - PURPOSE: TAS-102 is a combination of the thymidine-based nucleoside analog trifluridine and the thymidine phosphorylase inhibitor tipiracil. Efficacy and safety of TAS-102 in patients with metastatic colorectal cancer (mCRC) refractory or intolerant to standard therapies were evaluated in the phase 3 RECOURSE trial. Results of RECOURSE demonstrated significant improvement in overall survival (OS) and progression-free survival (PFS) with TAS-102 versus placebo [hazard ratio (HR) = 0.68 and 0.48 for OS and PFS, respectively; both P < 0.001]. The current analysis evaluates efficacy and safety of TAS-102 in the RECOURSE Spanish subgroup. METHODS: Primary and key secondary endpoints were evaluated in a post hoc analysis of the RECOURSE Spanish subgroup, using univariate and multivariate analyses. Safety and tolerability were reported with descriptive statistics. RESULTS: The RECOURSE Spanish subgroup included 112 patients (mean age 61 years, 62 % male). Median OS was 6.8 months in the TAS-102 group (n = 80) versus 4.6 months in the placebo group (n = 32) [HR = 0.47; 95 % confidence interval (CI): 0.28-0.78; P = 0.0032). Median PFS was 2.0 months in the TAS-102 group and 1.7 months in the placebo group (HR = 0.47; 95 % CI: 0.30-0.74; P = 0.001). Eighty (100 %) TAS-102 versus 31 (96.9 %) placebo patients had adverse events (AEs). The most common drug-related >/=Grade 3 AE was neutropenia (40 % TAS-102 versus 0 % placebo). There was 1 (1.3 %) case of febrile neutropenia in the TAS-102 group versus none in the placebo group. CONCLUSIONS: In the RECOURSE Spanish subgroup, TAS-102 was associated with significantly improved OS and PFS versus placebo, consistent with the overall RECOURSE population. No new safety signals were identified. CLINICALTRIALS. GOV STUDY NUMBER: NCT01607957. FAU - Longo-Munoz, F AU - Longo-Munoz F AD - Hospital Universitario Ramon y Cajal, Servicio Oncologia Medica, (Center Affiliated with the Red Tematica de Investigacion Cooperativa en Cancer, Instituto Carlos III, Spanish Ministry of Science and Innovation), Carretera de Colmenar Viejo Km 9.100, Madrid, Spain, 28034. FAU - Argiles, G AU - Argiles G AD - Hospital Universitario Vall d'Hebron, Universitat Autonoma de Barcelona, (Center Affiliated with the Red Tematica de Investigacion Cooperativa en Cancer, Instituto Carlos III, Spanish Ministry of Science and Innovation), P. Vall d'Hebron 119-129, 08035, Barcelona, Spain. FAU - Tabernero, J AU - Tabernero J AD - Hospital Universitario Vall d'Hebron, Universitat Autonoma de Barcelona, (Center Affiliated with the Red Tematica de Investigacion Cooperativa en Cancer, Instituto Carlos III, Spanish Ministry of Science and Innovation), P. Vall d'Hebron 119-129, 08035, Barcelona, Spain. FAU - Cervantes, A AU - Cervantes A AD - Biomedical Research Institute INCLIVA, University of Valencia, Av. Menendez Pelayo 4 accesorio, 46010, Valencia, Spain. FAU - Gravalos, C AU - Gravalos C AD - Hospital Universitario Doce de Octubre, Servicio Oncologia Medica, (Center Affiliated with the Red Tematica de Investigacion Cooperativa en Cancer, Instituto Carlos III, Spanish Ministry of Science and Innovation), Avenida Cordoba km 5.4, Madrid, Spain, 28041. FAU - Pericay, C AU - Pericay C AD - Hospital Universitario de Sabadell, Corporacio Sanitaria Parc Tauli, Parc Tauli, 1, 08208, Sabadell, Spain. FAU - Gil-Calle, S AU - Gil-Calle S AD - Hospital Carlos Haya, Av. de Carlos Haya, s/n, 29010, Malaga, Spain. FAU - Mizuguchi, H AU - Mizuguchi H AD - Taiho Oncology Inc, 202 Carnegie Center, Suite 100, Princeton, NJ, 08540, USA. FAU - Carrato-Mena, A AU - Carrato-Mena A AD - Hospital Universitario Ramon y Cajal, Servicio Oncologia Medica, (Center Affiliated with the Red Tematica de Investigacion Cooperativa en Cancer, Instituto Carlos III, Spanish Ministry of Science and Innovation), Carretera de Colmenar Viejo Km 9.100, Madrid, Spain, 28034. FAU - Limon, M L AU - Limon ML AD - Hospital Universitario Virgen del Rocio, S masculine Oncologia Medica, Manuel Siurot, 41013, Seville, Spain. FAU - Garcia-Carbonero, R AU - Garcia-Carbonero R AD - Hospital Universitario Doce de Octubre, Servicio Oncologia Medica, (Center Affiliated with the Red Tematica de Investigacion Cooperativa en Cancer, Instituto Carlos III, Spanish Ministry of Science and Innovation), Avenida Cordoba km 5.4, Madrid, Spain, 28041. rgcarbonero@gmail.com. LA - eng SI - ClinicalTrials.gov/NCT01607957 PT - Clinical Trial, Phase III PT - Comparative Study PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial DEP - 20160721 PL - Italy TA - Clin Transl Oncol JT - Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico JID - 101247119 RN - 0 (Antiviral Agents) RN - 0 (Drug Combinations) RN - 0 (Pyrrolidines) RN - 0 (trifluridine tipiracil drug combination) RN - 56HH86ZVCT (Uracil) RN - QR26YLT7LT (Thymine) RN - RMW9V5RW38 (Trifluridine) SB - IM MH - Adult MH - Aged MH - Aged, 80 and over MH - Antiviral Agents/therapeutic use MH - Colorectal Neoplasms/*drug therapy/secondary MH - Double-Blind Method MH - Drug Combinations MH - Drug Therapy, Combination MH - Female MH - Follow-Up Studies MH - Humans MH - Male MH - Middle Aged MH - Neoplasm Staging MH - Palliative Care MH - Prognosis MH - Pyrrolidines MH - Spain MH - Survival Rate MH - Thymine MH - Trifluridine/*therapeutic use MH - Uracil/*analogs & derivatives/therapeutic use PMC - PMC5239803 OTO - NOTNLM OT - Fluoropyrimidine OT - Metastatic colorectal cancer OT - Spain OT - TAS-102 OT - Tipiracil hydrochloride OT - Trifluridine COIS- Author A reports employment at Taiho Oncology Inc. Author B reports providing scientific advice to Bayer. Author C reports consulting/advisory fees from Amgen, Boehringer Ingelheim, Celgene, Chugai, Imclone Systems Inc., Eli Lilly and Company, Merck & Co., Merck Serono, Millennium, Novartis, F. Hoffmann-La Roche Ltd., Sanofi, Symphogen, and Taiho Oncology Inc. All other authors declare that they have no conflicts of interest. Informed consent Informed consent was obtained from all individual participants included in the study. Research involving human participants All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. EDAT- 2016/07/23 06:00 MHDA- 2017/02/15 06:00 PMCR- 2016/07/21 CRDT- 2016/07/23 06:00 PHST- 2016/03/02 00:00 [received] PHST- 2016/06/20 00:00 [accepted] PHST- 2016/07/23 06:00 [pubmed] PHST- 2017/02/15 06:00 [medline] PHST- 2016/07/23 06:00 [entrez] PHST- 2016/07/21 00:00 [pmc-release] AID - 10.1007/s12094-016-1528-7 [pii] AID - 1528 [pii] AID - 10.1007/s12094-016-1528-7 [doi] PST - ppublish SO - Clin Transl Oncol. 2017 Feb;19(2):227-235. doi: 10.1007/s12094-016-1528-7. Epub 2016 Jul 21.