title: 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.
abstract: OBJECTIVE
  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.
  NCT01607957.
authors.affiliation: Hospital Universitario Ramón y Cajal, Servicio Oncología Médica, (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.
authors.forename: F
authors.initials: F
authors.lastname: Longo-Muñoz
authors.affiliation: Hospital Universitario Vall d'Hebron, Universitat Autònoma 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.
authors.forename: G
authors.initials: G
authors.lastname: Argiles
authors.affiliation: Hospital Universitario Vall d'Hebron, Universitat Autònoma 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.
authors.forename: J
authors.initials: J
authors.lastname: Tabernero
authors.affiliation: Biomedical Research Institute INCLIVA, University of Valencia, Av. Menéndez Pelayo 4 accesorio, 46010, Valencia, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Cervantes
authors.affiliation: Hospital Universitario Doce de Octubre, Servicio Oncología Médica, (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.
authors.forename: C
authors.initials: C
authors.lastname: Gravalos
authors.affiliation: Hospital Universitario de Sabadell, Corporació Sanitària Parc Tauli, Parc Taulí, 1, 08208, Sabadell, Spain.
authors.forename: C
authors.initials: C
authors.lastname: Pericay
authors.affiliation: Hospital Carlos Haya, Av. de Carlos Haya, s/n, 29010, Málaga, Spain.
authors.forename: S
authors.initials: S
authors.lastname: Gil-Calle
authors.affiliation: Taiho Oncology Inc, 202 Carnegie Center, Suite 100, Princeton, NJ, 08540, USA.
authors.forename: H
authors.initials: H
authors.lastname: Mizuguchi
authors.affiliation: Hospital Universitario Ramón y Cajal, Servicio Oncología Médica, (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.
authors.forename: A
authors.initials: A
authors.lastname: Carrato-Mena
authors.affiliation: Hospital Universitario Virgen del Rocío, Sº Oncologia Medica, Manuel Siurot, 41013, Seville, Spain.
authors.forename: M L
authors.initials: ML
authors.lastname: Limón
authors.affiliation: Hospital Universitario Doce de Octubre, Servicio Oncología Médica, (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.
authors.forename: R
authors.initials: R
authors.lastname: Garcia-Carbonero
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000998:Antiviral Agents / Q000627:therapeutic use; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000556:secondary; D004311:Double-Blind Method; D004338:Drug Combinations; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D010166:Palliative Care; D011379:Prognosis; D011759:Pyrrolidines; D013030:Spain; D015996:Survival Rate; D013941:Thymine; D014271:Trifluridine / Q000627:therapeutic use*; D014498:Uracil / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: D000998:Antiviral Agents; D004338:Drug Combinations; D011759:Pyrrolidines; C000613803:trifluridine tipiracil drug combination; D014498:Uracil; D013941:Thymine; D014271:Trifluridine
keywords: Fluoropyrimidine; Metastatic colorectal cancer; Spain; TAS-102; Tipiracil hydrochloride; Trifluridine