Survival, safety, and prognostic factors for outcome with Regorafenib in patients with metastatic colorectal cancer refractory to standard therapies: results from a multicenter study (REBECCA) nested within a compassionate use program

BMC Cancer

Research Article

Stéphanie Clisant¹  David Tougeron²  Jean-Marc Phelip³  Christelle de la Fouchardiere⁴  Antoine Adenis⁵  Louis-Marie Dourthe⁶  Pascal Burtin⁷  Pierre-Luc Etienne⁸  Bernard Paule⁹  Thierry Andre^1,10  Andrew Kramar^1,11  Jennifer Wallet^1,11  Laurent Mineur^1,12 

[1] Clinical Research Unit, Centre Oscar Lambret, Lille, France;Gastroenterology, University Hospital, Poitiers, France;Gastroenterology, University Hospital, Saint Etienne, France;Medical Oncology, Centre Léon Bérard, Lyon, France;Medical Oncology, Centre Oscar Lambret and Catholic University, Lille, France;Department of Medical Oncology, Centre Oscar Lambret, 3, rue F Combemale, 59000, Lille, France;Medical Oncology, Clinique Sainte Anne, Strasbourg, France;Medical Oncology, Gustave Roussy, Villejuif, France;Medical Oncology, Hopital Privé des Côtes d’Armor, Plérin, France;Medical Oncology, Paul Brousse University Hospital, Villejuif, France;Medical Oncology, Saint Antoine Hospital, and University Pierre et Marie Curie (UMPC), Paris VI, Paris, France;Methodology and Biostatistics, Centre Oscar Lambret, Lille, France;Radiation and Medical Oncology, Institut Sainte-Catherine, Avignon, France;

关键词: Colorectal cancer;    Metastatic disease;    Regorafenib;    Antiangiogenic;    Cohort study;   

DOI  :  10.1186/s12885-016-2440-9

 received in 2015-10-29, accepted in 2016-06-22,  发布年份 2016

来源: Springer

【 摘 要 】

BackgroundRandomized trials have shown a survival benefit for regorafenib over placebo in patients with metastatic colorectal cancer (mCRC) that progressed after standard therapies. We evaluated survival and safety outcomes in patients treated with regorafenib in a real-life setting.MethodsREBECCA is a cohort study nested within a compassionate use program designed to evaluate survival, safety, and potential prognostic factors for outcome associated with regorafenib in patients with mCRC refractory to standard therapies. Treatment effects according to various patient and tumour characteristics were evaluated using univariate and multivariate Cox proportional hazards regression models.ResultsOf 1178 patients in the compassionate use program, 654 were in the full analysis set. Median follow-up was 16.5 months. Median survival was 5.6 months. The 12-month survival rate was 22 %. Survival was independently and unfavourably affected by the following variables: poor performance status, short time from initial diagnosis of metastases to the start of regorafenib, low initial regorafenib dose, >3 metastatic sites, presence of liver metastases, and KRAS mutations. We identified prognostic groups of patients with low, intermediate, and high risk of death, with a median survival of 9.2, 5.2, and 2.5 months, respectively. Five-hundred-twenty-four patients (80 %) experienced at least one regorafenib-related adverse event, most commonly, fatigue, hand-foot skin reaction, diarrhea, anorexia, arterial hypertension, and mucositis.ConclusionThe safety and efficacy profile of regorafenib in REBECCA are similar to those in randomized trials. Our prognostic model identified subgroups of mCRC patients who derived a minimal and maximum benefit from regorafenib.Trial registrationClinicaltrials.gov NCT02310477.

【 授权许可】

CC BY   
© The Author(s). 2016