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 Anti-Cancer Agents & Biologic Therapy
Supportive Care
Colon Cancer
Rectal Cancer
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.