Adjuvant Regorafenib in Stage IV Colorectal Cancer (CRC) After Curative Treatment of Liver Metastases: A Phase III Randomized, Placebo-Controlled Study (COAST)

Background: Complete resection and pre-/peri-/post-operative chemotherapy are the standard of care for patients with stage IV CRC and resectable metastases confined to the liver. Despite this treatment approach, long-term disease-free survival of patients with resected liver metastases is poor. The oral multikinase inhibitor REG significantly improved overall survival (OS) in patients with metastatic CRC that had progressed after all standard therapies (CORRECT study; HR 0.77; one-sided p = 0.0052; Lancet 2013). COAST will evaluate the efficacy and safety of REG vs PBO in patients with CRC after curative resection of liver metastases and completion of planned chemotherapy. Trial design: This double-blind, PBO-controlled, multicenter, phase III study (ClinicalTrials.gov identifier NCT01939223) will randomize patients (n = 750 planned) 1 : 1 to treatment with oral REG 160 mg or PBO once daily in 4-week cycles of 3 weeks on, 1 week off treatment. Doses of study drug may be delayed or reduced to manage clinically significant drug-related toxicities. Treatment will continue for 2 years or until recurrence of CRC, death, intolerable toxicity, or patient/investigator decision to stop. Inclusion criteria include age ≥18 years, stage IV CRC, pathology-proven complete resection of liver metastases, and ECOG performance status 0 or 1. Patients must have completed adjuvant, neoadjuvant, or perioperative chemotherapy. Randomization will be stratified by number of preoperative liver metastases ( 6 months), and time since last surgery for any CRC lesion (≤6 months vs >6 months). The primary endpoint is disease-free survival (DFS), assessed by the investigator using computed tomography or magnetic resonance imaging. Secondary endpoints include OS, health-related quality of life, and biomarker evaluations. Analyses will be performed when approximately 317 DFS events are observed, at which time the study will have 90% power to detect a 50% improvement in median DFS. The first patient entered the study in February 2014 and the estimated primary completion date is March 2018.Previously presented at WCGI 2014 abstract number: 749 (to be presented at WCGI 2014 as a poster presentation). Disclosure: A. Grothey: has the following financial disclosures: Advisory board: Bayer Corporate sponsored research: Bayer, Genentech, Eisai, Pfizer, ImClone, Daiichi; T. Yoshino: has the following financial disclosures: Corporate sponsored research: Daiichi Sankyo, Taiho, Bayer, Eli Lilly, Pfizer, Chugai, and Yakult; J. Zalcberg: has the following financial disclosures: Advisory board: Bayer, Roche Research and travel support, expert testimony: Bayer, Roche; D.J. Sargent: has the following financial disclosures: Advisory board: Bayer, Roche Corporate sponsored research: Roche, Celgene; M. Choti: has the following financial disclosures: Research consultant: Bristol Myers Squibb; M. Rutstein: has the following financial disclosures: Employment: Bayer HealthCare; L. Cupit: has the following financial disclosures: Employment: Bayer; I. Kuss: has the following financial disclosures: Employment: Bayer Pharma AG; E. Van Cutsem: has the following financial disclosures: Corporate sponsored research: Bayer . All other authors have declared no conflicts of interest.