Efficacy and Safety of Enzalutamide and Abiraterone in CRPC Patients With a History of Other Cancers: A Sub‐Analysis of the ENABLE Study for PCa

Objectives The ENABLE study, an investigator‐initiated, multicenter, randomized controlled trial, demonstrated comparable survival benefits between enzalutamide (ENZ) and abiraterone plus prednisolone (ABI) for castration‐resistant prostate cancer (CRPC). Because randomized controlled trials typically exclude patients with a history of other cancers (HOCs), we evaluated the efficacy of these agents in this population. Methods This sub‐analysis was conducted as a post hoc analysis using data from the ENABLE study. Endpoints included time to PSA progression, radiographic progression‐free survival, overall survival (OS), prostate cancer‐specific survival, and safety. Outcomes were compared between patients with and without a HOC+ versus HOC− and between treatment arms within each group. Results The HOC+ group included 35 patients (13 ENZ, 22 ABI), whereas the HOC− group included 149 patients (79 ENZ, 70 ABI). The most frequent malignancy was gastric cancer ( n = 10, 29%). HOC+ patients had significantly worse OS than HOC− patients (median 24.7 vs. 37.4 months; HR 1.96; 95% CI 1.02–3.77; p = 0.0426), while other survival endpoints did not differ between the groups. Within the HOC+ group, OS was significantly worse with ENZ than with ABI (median 16.0 vs. 30.5 months; HR 3.27; 95% CI 1.08–9.89; p = 0.0354), whereas no significant differences were observed between the arms in the HOC− group. Conclusions Although OS was poorer in HOC+ patients, other outcomes were similar, supporting the feasibility of ENZ and ABI regardless of cancer history. The longer OS with ABI in HOC+ patients represents a hypothesis‐generating observation and should be interpreted with particular caution.