Purpose: To determine which sequence of abiraterone (ABI) and enzalutamide (ENZA) shows better survival outcomes in Veterans diagnosed with metastatic castration-resistant prostate cancer (mCRPC) at VA San Diego.
Background: Prostate cancer is the leading cancer diagnosis among American men who eventually develop mCRPC. Therapies for mCRPC include androgen receptor pathway inhibitors like ABI and ENZA. Both improve survival independently; however, the optimal treatment sequence has not been determined. Retrospective studies have shown that the ABI-ENZA sequence significantly improves progression-free survival (PFS) and combined prostate-specific antigen PFS (cPSA-PFS), but not overall survival (OS).
Methods: A retrospective chart review was conducted in subjects with mCRPC who had received ABI and ENZA sequentially in either order. Subjects must have received at least one month of each drug; those who had an interruption of treatment sequence were excluded. The primary outcomes were to compare cPSA-PFS and OS between the two sequences; cPSA-PFS represented time from start of drug 1 to > 25% PSA increase from baseline/nadir on drug 2, while OS represented time from start of drug 1 to death from any cause. OS and cPSA-PFS were reported via Kaplan-
Meier curves and hazard ratios (HR). Ninety-eight subjects per group were needed to reach 80% power for an effect size of 0.404 in cPSA-PFS.
Results: Forty subjects were identified and 8 were excluded; of the remaining, 9 received ENZA-ABI and 23 received ABIENZA. Baseline characteristics were similar. There were no differences in cPSA-PFS between ENZA-ABI and ABI-ENZA: median 406 days versus 534 days (HR 1.39, 95% CI 0.59-1.53, P = .59), respectively. OS did not differ between ENZAABI and ABI-ENZA: median 711 days versus 803 days (HR 0.88, 95% CI 0.35-1.59, P = .21), respectively.
Conclusions: There were no significant differences in outcomes between sequences although ABI-ENZA showed longer cPSA-PFS and OS. This is consistent with previous studies where ABI-ENZA had significantly longer PFS and cPSA-PFS; ABI-ENZA OS was longer but not significantly different in those studies. Limitations included a small sample size and uneven groups. Ultimately, ABI-ENZA should be considered as the sequence-of-choice for treatment of mCRPC until prospective studies confirm the optimal sequence.
