Phase III Study of Cabozantinib in Previously Treated Metastatic Castration-Resistant Prostate Cancer: COMET-1.
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Embargo End Date
ICR Authors
Authors
Smith, M
De Bono, J
Sternberg, C
Le Moulec, S
Oudard, S
De Giorgi, U
Krainer, M
Bergman, A
Hoelzer, W
De Wit, R
Bögemann, M
Saad, F
Cruciani, G
Thiery-Vuillemin, A
Feyerabend, S
Miller, K
Houédé, N
Hussain, S
Lam, E
Polikoff, J
Stenzl, A
Mainwaring, P
Ramies, D
Hessel, C
Weitzman, A
Fizazi, K
De Bono, J
Sternberg, C
Le Moulec, S
Oudard, S
De Giorgi, U
Krainer, M
Bergman, A
Hoelzer, W
De Wit, R
Bögemann, M
Saad, F
Cruciani, G
Thiery-Vuillemin, A
Feyerabend, S
Miller, K
Houédé, N
Hussain, S
Lam, E
Polikoff, J
Stenzl, A
Mainwaring, P
Ramies, D
Hessel, C
Weitzman, A
Fizazi, K
Document Type
Journal Article
Date
2016-09-01
Date Accepted
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.
Citation
Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 2016, 34 (25), pp. 3005 - 3013
Source Title
Publisher
LIPPINCOTT WILLIAMS & WILKINS
ISSN
0732-183X
eISSN
1527-7755
Collections
Research Team
Prostate Cancer Targeted Therapy Group