Traditionally, agents for the treatment of metastatic castrate-resistant prostate cancer (mCRPC) have been used sequentially rather than in combination. The combination of abiraterone acetate, prednisone, and cabazitaxel is an intriguing approach to concurrent use of both hormone-directed therapy and a cytotoxic approach. We congratulate Dr Massard and his colleagues on the recent publication of results of a phase I/II trial of cabazitaxel plus abiraterone acetate and prednisone in 37 patients with mCRPC after prior docetaxel and abiraterone acetate [1]. They found that the combination was well tolerated at the approved doses for both drugs, with a toxicity profile that is consistent with the established safety profiles of cabazitaxel and abiraterone acetate/prednisone separately. The primary endpoint was PSA response rate (PSA response defined as >/= 50% reduction in PSA). Even though an absolute difference of 25% increase in PSA response rate (RR) was not observed (null hypothesis of 25% PSA RR; alternative hypothesis of 50% PSA RR), the combination of cabazitaxel and abiraterone showed a PSA RR of 46%, RECIST radiographic objective response rate (ORR) of 21%, and median progression-free survival (mPFS) of 6.9 months. For comparison, in the TROPIC study [2], cabazitaxel monotherapy showed a PSA RR of 39%, ORR 14.4%, and mPFS of 2.8 months. In the COU-AA-301 study of abiraterone acetate post docetaxel [3], PSA RR was 29%, ORR was 14%, and mPFS was 5.6 months.
At the University of Colorado Cancer Centre, in an attempt to build upon the results of the TROPIC study and to inform on the potential utility of sequencing these agents or combination therapies, we conducted a study to evaluate the efficacy of cabazitaxel with or without abiraterone acetate and prednisone (ClinicalTrials.gov: NCT01845792). Eleven patients were screened and seven patients were enrolled. Two patients received cabazitaxel monotherapy and five patients received the combination of abiraterone acetate plus cabazitaxel. No statistics or firm conclusions can be made on the basis of such small numbers, but the trend clearly favoured the combination as in the Massard et al. publication.
Our single centre study was closed due to poor accrual. Despite the small number of patients and insufficient power to calculate statistical significance, our experience with the combination of abiraterone acetate and cabazitaxel in mCRPC patients were similar to the study completed by Massard et al. With the approvals of multiple agents with overall survival benefit since 2010, the challenge currently is to determine the proper sequential or combination use of these agents. Our study and that of Massard et al. highlight the potential benefits of the combination of cabazitaxel with abiraterone acetate and prednisone in patients with mCRPC.
Funding
Clinical trial funding was provided by Janssen Pharmaceuticals. Dr. Lam received funding from the National Cancer Institute Paul Calabresi Award in Clinical Oncology Research (K12CA086913).
Disclosure
TWF received institutional clinical trial research support from Janssen, Cougar, and Sanofi. ETL received institutional clinical trial research support from Janssen. All remaining authors have declared no conflicts of interest.
References
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