| Added by | mollevi |
|---|---|
| Last modified by | celine.gongora |
| Group name | EquipeCG |
| Item Type | Journal Article |
| Title | Phase III Study of Cabozantinib in Previously Treated Metastatic Castration-Resistant Prostate Cancer: COMET-1 |
| Creator | Smith et al. |
| Author | M. Smith |
| Author | J. De Bono |
| Author | C. Sternberg |
| Author | S. Le Moulec |
| Author | S. Oudard |
| Author | U. De Giorgi |
| Author | M. Krainer |
| Author | A. Bergman |
| Author | W. Hoelzer |
| Author | R. De Wit |
| Author | M. Bogemann |
| Author | F. Saad |
| Author | G. Cruciani |
| Author | A. T. Vuillemin |
| Author | S. Feyerabend |
| Author | K. Miller |
| Author | N. Houede |
| Author | S. Hussain |
| Author | E. Lam |
| Author | J. Polikoff |
| Author | A. Stenzl |
| Author | P. Mainwaring |
| Author | D. Ramies |
| Author | C. Hessel |
| Author | A. Weitzman |
| Author | K. Fizazi |
| Abstract | PURPOSE: Cabozantinib is an inhibitor of kinases, including MET and vascular endothelial growth factor receptors, and has shown activity in men with previously treated metastatic castration-resistant prostate cancer (mCRPC). This blinded phase III trial compared cabozantinib with prednisone in patients with mCRPC. PATIENTS AND METHODS: Men with progressive mCRPC after docetaxel and abiraterone and/or enzalutamide were randomly assigned at a two-to-one ratio to cabozantinib 60 mg once per day or prednisone 5 mg twice per day. The primary end point was overall survival (OS). Bone scan response (BSR) at week 12 as assessed by independent review committee was the secondary end point; radiographic progression-free survival (rPFS) and effects on circulating tumor cells (CTCs), bone biomarkers, serum prostate-specific antigen (PSA), and symptomatic skeletal events (SSEs) were exploratory assessments. RESULTS: A total of 1,028 patients were randomly assigned to cabozantinib (n = 682) or prednisone (n = 346). Median OS was 11.0 months with cabozantinib and 9.8 months with prednisone (hazard ratio, 0.90; 95% CI, 0.76 to 1.06; stratified log-rank P = .213). BSR at week 12 favored cabozantinib (42% v 3%; stratified Cochran-Mantel-Haenszel P < .001). rPFS was improved in the cabozantinib group (median, 5.6 v 2.8 months; hazard ratio, 0.48; 95% CI, 0.40 to 0.57; stratified log-rank P < .001). Cabozantinib was associated with improvements in CTC conversion, bone biomarkers, and post-random assignment incidence of SSEs but not PSA outcomes. Grade 3 to 4 adverse events and discontinuations because of adverse events were higher with cabozantinib than with prednisone (71% v 56% and 33% v 12%, respectively). CONCLUSION: Cabozantinib did not significantly improve OS compared with prednisone in heavily treated patients with mCRPC and progressive disease after docetaxel and abiraterone and/or enzalutamide. Cabozantinib had some activity in improving BSR, rPFS, SSEs, CTC conversions, and bone biomarkers but not PSA outcomes. |
| Publication | J Clin Oncol |
| Date | Jul 11 2016 |
| Journal Abbr | Journal of clinical oncology : official journal of the American Society of Clinical Oncology |
| DOI | 10.1200/JCO.2015.65.5597 |
| ISSN | 1527-7755 (Electronic) 0732-183X (Linking) |
| Tags | clinic, exelixis |
| Date Added | 2018/07/20 - 10:05:58 |
| Date Modified | 2019/10/24 - 17:43:37 |
| Notes and Attachments | (Note) (Note) 27400947 (Attachment) |
Institut de Recherche en Cancérologie de
