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    Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2016 Jul 11. pii: JCO.2015.65.5597. doi: 10.1200/JCO.2015.65.5597
    Phase III Study of Cabozantinib in Previously Treated Metastatic Castration-Resistant Prostate Cancer: COMET-1.
    Smith M1,  De Bono J2,  Sternberg C3,  Le Moulec S4,  Oudard S5,  De Giorgi U6,  Krainer M7,  Bergman A8,  Hoelzer W9,  De Wit R10,  Bögemann M11,  Saad F12,  Cruciani G13,  Vuillemin AT14,  Feyerabend S15,  Miller K16,  Houédé N17,  Hussain S18,  Lam E19,  Polikoff J20,  Stenzl A21,  Mainwaring P22,  Ramies D23,  Hessel C24,  Weitzman A25,  Fizazi K26
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    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.


    © 2016 by American Society of Clinical Oncology.

    Publikations ID: 27400947
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