LBA18 - Phase 3 CORRECT trial of regorafenib in metastatic colorectal cancer (mCRC): Overall survival update

Date 01 October 2012
Event ESMO Congress 2012
Session Gastrointestinal tumors, colorectal
Topics Anti-Cancer Agents & Biologic Therapy
Colon Cancer
Rectal Cancer
Presenter Eric Van Cutsem
Authors E. Van Cutsem1, A. Grothey2, A. Sobrero3, S. Siena4, A. Falcone5, M. Ychou6, Y. Humblet7, O. Bouché8, L. Mineur9, C. Barone10, A. Adenis11, J. Tabernero12, T. Yoshino13, H. Lenz14, R. Goldberg15, D. Sargent16, F. Cihon17, L. Cupit18, A. Wagner19, D. Laurent20
  • 1Digestive Oncology, Leuven Cancer Institute (LKI), University Hospital Gasthuisberg, Leuven/BE
  • 2Medical Oncology, Mayo Clinic, US-55905 - Rochester/US
  • 3Oncologia Medica, Azienda Ospedaliera Universitaria S. Martino di Genova, Genova/IT
  • 4The Falck Division Of Medical Oncology, Ospedale Niguarda Ca’ Granda, Milan/IT
  • 5Dept. Of Oncology-presidio Ospedaliero, Azienda Ospedaliero Univesitaria Pisana, IT-56100 - Pisa/IT
  • 6Oncologie Médicale Digestive, Centre Val d'Aurelle, Montpellier/FR
  • 7Medical Oncology Dept, St-Luc Hospital, Centre du Cancer, Universití Catholique de Louvain, Brussels/BE
  • 8Centre Hospitalier Universitaire Robert Debré, Reims/FR
  • 9Gastrointestinal And Liver Oncology–radiotherapy Unit, Institut Sainte-Catherine, Avignon/FR
  • 10Division Of Medical Oncology, Catholic University of Sacred Heart, Rome/IT
  • 11Centre Oscar Lambret, Lille/FR
  • 12Medical Oncology Department, Vall d'Hebron University Hospital, ES-08035 - Barcelona/ES
  • 13Gastroenterology & Gastrointestinal Oncology, National Cancer Center Hospital East, 277-8577 - Kashiwa/JP
  • 14Norris Comprehensive Cancer Center, University of Southern California, Los Angeles/US
  • 15Division Of Medical Oncology, Ohio State University School of Medicine, James Cancer Hospital and Solove Research Institute, Columbus/US
  • 16N/a, Mayo Clinic, Rochester/US
  • 17Clinical Statistics, Bayer HealthCare Pharmaceuticals, Montville/US
  • 18N7a, Bayer Healthcare Pharmaceuticals, Montville/US
  • 19Global Clinical Development Oncology 2, Bayer HealthCare Pharmaceuticals, Berlin/DE
  • 20-, Bayer Pharma AG, Berlin/DE

Abstract

Background: The CORRECT trial was conducted to evaluate the oral multikinase inhibitor regorafenib (REG) in patients ( pts) with mCRC whose disease had progressed after all approved standard therapies. This trial met its primary endpoint at a pre-planned interim analysis, the results of which were presented previously
(J Clin Oncol 30, 2012 [suppl; abstr 3502]). The updated overall survival (OS) data are reported here.

Methods: Enrollment criteria included documented mCRC and progression during or ≤3 months after last standard therapy. Pts were randomized 2:1 to receive best supportive care plus either REG (160 mg od po) or placebo (PL) on a 3 weeks on/1 week off schedule. The primary endpoint was overall survival (OS). Secondary endpoints included progression-free survival (PFS), overall response rate, and disease control rate. Safety and quality of life were also evaluated.

Results: From May 2010 to March 2011, 760 pts were randomized (REG: 505; PL: 255). Baseline characteristics were balanced between the two arms. A descriptive updated analysis of OS was performed, based on a database cutoff of Nov 13, 2011 with 566 total events (97% of events originally required). In this analysis, the hazard ratio (HR, REG/PL) for OS was 0.79 (95% CI, 0.66-0.94, 1-sided p = 0.0038). Median OS was 6.4 months (95% CI, 5.8-7.0) in the REG arm vs 5.0 months (95% CI,
4.4-5.9) in the PL arm. OS rate at 6 and 12 months was 52.2% and 24.1% in the REG arm vs 43.1% and 17% in the PL arm, respectively. These data serve as an update to previously reported OS data from the earlier interim analysis based on 432
(74%) events, which showed a HR for OS of 0.77 (95% CI, 0.64-0.94, 1-sided p = 0.0052). Pts in the REG arm received an average of 78.9% of the planned dose, and pts in PL arm 90.2% of the planned dose. The mean treatment duration was 12.1 ± 9.7 wks (REG) and 7.8 ± 5.2 wks (PL), respectively. Incidence of
treatment-emergent, REG-related adverse events was similar in subgroups by age, sex, renal function and hepatic function, whereas the incidence was higher in Asian pts (98.6%) compared with Caucasian pts (92.3%), and higher in pts with a baseline
ECOG score of 0 (97.0%) compared with pts with ECOG score of 1 (88.6%).

Conclusions: This updated OS analysis demonstrated the robustness and consistency of the OS benefit of REG treatment over PL in pts with previously treated mCRC.

Disclosure: E. Van Cutsem: Received research funding from Bayer A. Grothey: Mayo Clinic received research funding and honoraria for my consulting activity from Bayer, Genentech, Sanofi, Bayer, Daiichi, Imclone. Onyx and BMS A. Sobrero: Advisory board member and has spoken at symposia for: Roche, Merck, Bayer,
Amgen, Sanofi S. Siena: Advisory board member for Amgen, AstraZeneca, Bayer, Genentech, Merck-Serono, Roche, Sanofi A. Falcone: Received honoraria from Bayer for speaking, consultancy and sitting on advisory boards. Also received research support from Bayer M. Ychou: Received honoraria from Bayer for sitting on advisory board Y. Humblet: Has received honoraria from Bayer to act as consultant. Has also received research funding from Bayer O. Bouche: Received honoraria from Roche, Merck-Sereno, Amgen L. Mineur: No conflicts of interest to declare C. Barone:
Received honoraria for lecturing and advisory boards from Bayer, Merck, Roche, Novartis. Received honoraria for lecturing from GlaxoSmithKline, Amgen A. Adenis: Received honoraria from Bayer (conference and research funding) J. Tabernero: No
conflicts of interest to declare T. Yoshino: Received consulting fee from Takeda; honoraria from Chugai, Takeda, Yakult, Bristol-Meyers Squibb and Merck-Serono; research funding from Daiichi Sankyo, Taiho, Bayer and Imclone H-J. Lenz: No conflicts of interest to declare R. Goldberg: Research support to hip State University from Sanofi, Bayer, Myriad, Jennerex. Consulting (unpaid) for Bayer, Sanofi. Payment for a Data Safety Monitoring Board, Lilly D. Sargent: Consulting fees from the CORRECT steering committee of <$5000/year F. Cihon: Employee of Bayer
(sponsor of the study) L. Cupit: Employee of Bayer (sponsor of the study) A. Wagner: Employee of Bayer (sponsor of the study) D. Laurent: Employee of Bayer (sponsor of the study) All other authors have declared no conflicts of interest.