LBA13 - Phase III RECOURSE trial of TAS-102 vs. placebo, with best supportive care (BSC), in patients (pts) with metastatic colorectal cancer (mCRC) refrac...

Date 27 September 2014
Event ESMO 2014
Session Gastrointestinal tumours, colorectal
Topics Anticancer agents
Supportive Measures
Colon and Rectal Cancer
Therapy
Biological Therapy
Presenter Eric Van Cutsem
Citation Annals of Oncology (2014) 25 (5): 1-41. 10.1093/annonc/mdu438
Authors E. Van Cutsem1, A. Ohtsu2, A. Falcone3, T. Yoshino4, R. Garcia-Carbonero5, N. Mizunuma6, K. Yamazaki7, Y. Shimada8, J. Tabernero9, Y. Komatsu10, A. Sobrero11, E. Boucher12, M. Peeters13, B. Tran14, H. Lenz15, A. Zaniboni16, H. Hochster17, M. Aivado18, L. Makris19, R. Mayer20
  • 1Internal Medicine, University Hospital Gasthuisberg, 3000 - Leuven/BE
  • 2Research Center For Innovative Oncology, National Cancer Center Hospital East, JP-277-8577 - Kashiwa/JP
  • 3Dept. Of Translational Research And New Technologies In Medicine, University of Pisa, IT-56100 - Pisa/IT
  • 4Gastroenterology & Gastrointestinal Oncology, National Cancer Center Hospital East, 277-8577 - Kashiwa/JP
  • 5Oncology Department, Hospital Universitario Virgen del Rocio, IBIS/ES
  • 6Gastroenterology, The Cancer Institute Hospital of Japanese Foundation for Cancer Research, 135-8550 - Koto-ku/JP
  • 7Gastrointestinal Oncology And Endoscopy, Shizuoka Cancer Center, 411-8777 - Shizuoka/JP
  • 8Gastrointestinal Oncolgoy, National Cancer Center Hospital, Chuo-ku/JP
  • 9Medical Oncology / Gastrointestinal Tumors Group, Vall d'Hebron University Hospital, 08035 - Barcelona/ES
  • 10Cancer Center, Hokkaido University Hospital, Sapporo/JP
  • 11Oncologia Medica, Ospedale San Martino, 16132 - Genova/IT
  • 12Medical Oncology, Centre Eugène Marquis, Rennes cedex/FR
  • 13Department Of Oncology, Antwerp University Hospital, 2650 - Edegem/BE
  • 14Medical Oncology, The Royal Melbourne Hospital, Melbourne/AU
  • 15Cancer Geriatrics Unit, USC Norris Comprehensive Cancer Center, Los Angeles/US
  • 16Oncology Department, Fondazione Poliambulanza, IT-25124 - Brescia/IT
  • 17Medical Oncology, Yale Cancer Center, New Haven/US
  • 18Late Phase Clinical Development, And Pharmacovigilance, Taiho Onclogy, Inc., 08540 - Princeton/US
  • 19., Stathmi Inc., New Hope/US
  • 20Medical Oncology, Dana-Farber Cancer Institute, Boston/US

Abstract

Aim

TAS-102 is a combination of a novel oral nucleoside, trifluridine (FTD) with the thymidine phosphorylase inhibitor, tipiracil hydrochloride (TPI), which prevents the degradation of FTD, enabling sustained and effective FTD levels. RECOURSE (Sponsor: Taiho Oncology Inc. / Taiho Pharmaceutical Co. Ltd.) was conducted to evaluate the efficacy and safety of TAS-102 in pts with mCRC refractory to standard therapies.

Methods

mCRC-patients (ECOG PS 0-1) who failed fluoropyrimidines, irinotecan, oxaliplatin, bevacizumab and cetuximab/panitumumab (if KRAS wild-type) were eligible. The primary endpoint (overall survival, OS) and the key secondary efficacy endpoint (progression-free survival, PFS) were evaluated using univariate and multivariate analyses for prospectively defined subgroups and a retrospectively defined subgroup with prior regorafenib.

Results

800 pts were randomized to TAS-102 (534 pts) or placebo (266 pts). The hazard ratios for OS and PFS were 0.68 (95% CI: 0.58 - 0.81; p < 0.0001) and 0.48 (95% CI: 0.41 - 0.57; p < 0.0001), respectively, both favoring TAS-102. OS and PFS benefit for TAS-102 was consistent across all subgroups. OS treatment effect in the multivariate model remained the same. Safety results were previously presented [Yoshino T. et al., Ann Oncol 2014; 25 (Suppl 2; abstr O-0022)]. Time to worsening of ECOG PS status to 2 or more was significantly delayed with TAS-102 vs. placebo [medians of 5.7 vs. 4.0 months, HR = 0.66 (95% CI: 0.56–0.78)]. Post-study treatment was similar between arms (41.2% in TAS-102, 42.5% in placebo).

Subgroups OS
N HR 95% CI
KRAS status
Wild-type 393 0.58 0.45-0.74
Mutant 407 0.80 0.63-1.02
Region
Western 534 0.64 0.52-0.80
Asia 266 0.75 0.57-1.00
PS
0 448 0.73 0.58-0.93
1 352 0.61 0.48-0.79
Prior Use of regorafenib
Yes 144 0.69 0.45-1.05
No 656 0.69 0.57-0.83

Conclusions

OS and PFS benefit was observed in all prospectively defined subgroup analyses, including prior regorafenib therapy.

Disclosure

K. Yamazaki: Other substantive relationships (speakers bureaus) from Taiho Pharmaceutical Co., Ltd; Y. Shimada: Membership on an advisory board, Corporate-sponsored research finding, and Other substantive relationships (speakers bureaus) from Taiho Pharmaceutical Co., Ltd; M. Aivado: Sponsor's employee; L. Makris: Consulting engagement for Taiho Pharmaceutical Co. Ltd. and Taiho Oncology Inc. All other authors have declared no conflicts of interest.