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

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.