title: Efficacy, Safety and Cost of Regorafenib in Patients with Metastatic Colorectal Cancer in French Clinical Practice.
abstract: BACKGROUND
  Regorafenib is an orally administered multikinase inhibitor that has been approved for patients with chemotherapy-refractory metastatic colorectal cancer (mCRC). Even though regorafenib significantly improved survival in two international phase 3 trials (CORRECT and CONCUR), a high rate of treatment-related toxic effects and dose modifications were observed with a modest benefit. The aim of this study was to provide information concerning the efficacy, safety, and cost of regorafenib in patients with mCRC in clinical practice.
  
  
  METHODS
  We retrospectively reviewed patients treated with regorafenib monotherapy for unresectable mCRC in five Franche-Comté cancer hospitals (France). The primary end point was overall survival. Secondary end points were safety and descriptive cost analyses of patients treated with regorafenib in clinical practice. Another aim of this study was to assess the impact of regorafenib prescription on the risk of hospitalization in real-life practice.
  
  
  RESULTS
  From January 2014 to August 2014, 29 consecutive patients were enrolled. Patients were heavily pretreated and were refractory to standard chemotherapies. The primary tumor sites were the colon and the rectum for 55% and 45% of patients, respectively. Fifteen patients (51%) harbored an RAS mutation. Eastern Cooperative Oncology Group - Performance Status (PS) was 0-1 for 86% of patients and 2 for 14% of patients. Nineteen patients (66%) initially received reduced doses of 120 or 80 mg/day. The median duration of treatment was 2.5 months (range, 0.13-11.4 months). Treatment-related adverse events occurred in 86% of patients. The most frequent adverse events of any grade were fatigue (35%), diarrhea (20%), and hand-foot skin reaction (20%). Grade 3 or 4 treatment-related adverse events occurred in 10 patients (35%). Three patients (10%) were admitted to hospital due to drug-related severe adverse events. The mean cost of patient management with regorafenib for the duration of treatment was 9908 ± 8191€, and median cost was 7917€ (Interquartile range (IQR) 4469-13,042). The median overall survival was six months (95% confidence interval, five to eight months).
  
  
  CONCLUSIONS
  The safety and efficacy of regorafenib in heavily pretreated mCRC patients was comparable, in our study, to prospective and retrospective trials. Toxic effects were mostly manageable in an outpatient setting. Regorafenib itself represented the most important (93%) part of supported costs. Even though most side effects were manageable in an outpatient setting, severe adverse events occurred from hospitalization in 10% of patients. These data should be confirmed in a larger real-life-based cohort. Identification of predictive biomarkers is needed for mCRC patient selection for regorafenib treatment.
authors.affiliation: Department of Medical Oncology, Besançon University Hospital, Besançon, France.; INSERM, UMR 1098, Besançon, France.; University of Bourgogne-Franche-Comté, UMR 1098, SFR IBCT, Besançon, France.; Clinical Investigation Center, Inserm CIC 1431, Besançon, France.
authors.forename: Fabien
authors.initials: F
authors.lastname: Calcagno
authors.affiliation: Pharmacy Department, Besançon University Hospital, Besançon, France.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Lenoble
authors.affiliation: Liver Transplantation and Digestive Surgery Unit, Besançon University Hospital, Besançon, France.
authors.forename: Zaher
authors.initials: Z
authors.lastname: Lakkis
authors.affiliation: Department of Medical Oncology, Besançon University Hospital, Besançon, France.
authors.forename: Thierry
authors.initials: T
authors.lastname: Nguyen
authors.affiliation: University of Bourgogne-Franche-Comté, UMR 1098, SFR IBCT, Besançon, France.; Pharmacy Department, Besançon University Hospital, Besançon, France.
authors.forename: Samuel
authors.initials: S
authors.lastname: Limat
authors.affiliation: Department of Medical Oncology, Besançon University Hospital, Besançon, France.; INSERM, UMR 1098, Besançon, France.; University of Bourgogne-Franche-Comté, UMR 1098, SFR IBCT, Besançon, France.; Clinical Investigation Center, Inserm CIC 1431, Besançon, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Borg
authors.affiliation: Department of Medical Oncology, Besançon University Hospital, Besançon, France.; INSERM, UMR 1098, Besançon, France.; University of Bourgogne-Franche-Comté, UMR 1098, SFR IBCT, Besançon, France.; Clinical Investigation Center, Inserm CIC 1431, Besançon, France.
authors.forename: Marine
authors.initials: M
authors.lastname: Jary
authors.affiliation: Department of Medical Oncology, Besançon University Hospital, Besançon, France.; Clinical Investigation Center, Inserm CIC 1431, Besançon, France.
authors.forename: Stefano
authors.initials: S
authors.lastname: Kim
authors.affiliation: INSERM, UMR 1098, Besançon, France.; University of Bourgogne-Franche-Comté, UMR 1098, SFR IBCT, Besançon, France.; Pharmacy Department, Besançon University Hospital, Besançon, France.
authors.forename: Virginie
authors.initials: V
authors.lastname: Nerich
keywords: cost; efficacy; metastatic colorectal cancer; regorafenib; safety