Is Abiraterone Acetate More Effective With or Without Cabazitaxel for mCRPC?

By Emily Menendez - Last Updated: October 31, 2023

Gene expression profiling has shown that metastatic castration-resistant prostate cancer (mCRPC) cells are deficient in retinoblastoma proteins (RB), resulting in a hypersensitivity to taxanes such as cabazitaxel. Preclinical studies have found that cabazitaxel has superior antitumor efficacy compared with docetaxel for mCRPC. A phase 2, randomized trial investigated the potential efficacy of abiraterone acetate/prednisone plus cabazitaxel against abiraterone acetate/prednisone alone to determine if the combination can be utilized as a novel treatment for mCRPC.

The trial determined the radiographic progression-free survival (rPFS), prostate-specific antigen (PSA) PFS, overall objective response, and safety of abiraterone acetate/prednisone plus cabazitaxel in 81 patients with mCRPC. Equally allocated patients were administered abiraterone acetate/prednisone followed by switching to cabazitaxel upon radiographic progression in arm 1 of the trial. Patients in arm 2 were treated upfront with abiraterone acetate/prednisone plus cabazitaxel.

Patients were stratified into high- or low-risk groups based on the Halabi nomogram. The real-time assessment of RB status and circulating tumor cell (CTC) analysis to correlate with clinical outcomes was exploratory.

Treatment in both arms of the study was well-tolerated. The median rPFS of abiraterone acetate/prednisone alone was 6.4 months (95% CI, 3.8-10.6), and median overall survival (OS) was 18.3 months (95% CI, 14.4-37.6). A total of 56% of patients showed ≥50% decline in PSA.

The median rPFS of patients administered abiraterone acetate/prednisone plus cabazitaxel was 14.8 months (95% CI, 10.6-16.4), and the median OS was 24.5 months (95% CI, 20.4-35.0). There was a ≥50% decline in PSA in 92.1% of patients.

Neither RB expression in pretherapy tumor biopsy, CTC, or tissue explants identified those patients who may benefit from abiraterone acetate/prednisone plus cabazitaxel.

Abiraterone acetate/prednisone plus cabazitaxel administered earlier in treatment rather than sequentially may benefit some patients, as it was safe, with improved rPFS, OS duration, and a higher proportion of PSA declines. Further research is needed to define the patient population more closely.