title: 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.
abstract: Randomized 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.
  
  
  
  REBECCA 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.
  
  
  
  Of 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.
  
  
  
  The 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.
  
  
  
  Clinicaltrials.gov NCT02310477 .
authors.affiliation: Medical Oncology, Centre Oscar Lambret and Catholic University, Lille, France. a-adenis@o-lambret.fr.|Department of Medical Oncology, Centre Oscar Lambret, 3, rue F Combemale, 59000, Lille, France. a-adenis@o-lambret.fr.
authors.forename: Antoine
authors.initials: A
authors.lastname: Adenis
authors.affiliation: Medical Oncology, Centre Léon Bérard, Lyon, France.
authors.forename: Christelle
authors.initials: C
authors.lastname: de la Fouchardiere
authors.affiliation: Medical Oncology, Paul Brousse University Hospital, Villejuif, France.
authors.forename: Bernard
authors.initials: B
authors.lastname: Paule
authors.affiliation: Medical Oncology, Gustave Roussy, Villejuif, France.
authors.forename: Pascal
authors.initials: P
authors.lastname: Burtin
authors.affiliation: Gastroenterology, University Hospital, Poitiers, France.
authors.forename: David
authors.initials: D
authors.lastname: Tougeron
authors.affiliation: Methodology and Biostatistics, Centre Oscar Lambret, Lille, France.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Wallet
authors.affiliation: Medical Oncology, Clinique Sainte Anne, Strasbourg, France.
authors.forename: Louis-Marie
authors.initials: LM
authors.lastname: Dourthe
authors.affiliation: Medical Oncology, Hopital Privé des Côtes d'Armor, Plérin, France.
authors.forename: Pierre-Luc
authors.initials: PL
authors.lastname: Etienne
authors.affiliation: Radiation and Medical Oncology, Institut Sainte-Catherine, Avignon, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Mineur
authors.affiliation: Clinical Research Unit, Centre Oscar Lambret, Lille, France.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Clisant
authors.affiliation: Gastroenterology, University Hospital, Saint Etienne, France.
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Phelip
authors.affiliation: Methodology and Biostatistics, Centre Oscar Lambret, Lille, France.
authors.forename: Andrew
authors.initials: A
authors.lastname: Kramar
authors.affiliation: Medical Oncology, Saint Antoine Hospital, and University Pierre et Marie Curie (UMPC), Paris VI, Paris, France.
authors.forename: Thierry
authors.initials: T
authors.lastname: Andre
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D015331:Cohort Studies; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics; D057176:Compassionate Use Trials; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009362:Neoplasm Metastasis; D010671:Phenylurea Compounds / Q000008:administration & dosage* / Q000627:therapeutic use; D011379:Prognosis; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics*; D011725:Pyridines / Q000008:administration & dosage* / Q000627:therapeutic use; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; C117307:KRAS protein, human; D010671:Phenylurea Compounds; D011725:Pyridines; C559147:regorafenib; D016283:Proto-Oncogene Proteins p21(ras)
keywords: Antiangiogenic; Cohort study; Colorectal cancer; Metastatic disease; Regorafenib