JMA J. 2026 Sep 15;9(5):1350-1359. doi: 10.31662/jmaj.2026-0201. Epub 2026 Jul 31.
ABSTRACT
INTRODUCTION: The ENABLE study demonstrated comparable survival benefits between enzalutamide (ENZ) and abiraterone plus prednisolone (ABI) in castration-resistant prostate cancer (CRPC). Although the association between androgen receptor signaling inhibition and cardio-cerebrovascular diseases (CCVDs) has long been discussed, definitive evidence remains limited. We evaluated the efficacy of these agents in patients with CRPC who have CCVDs.
METHODS: This investigator-initiated, multicenter, randomized controlled trial allowed enrollment of patients with prior or concurrent CCVDs. Prespecified end points included time to prostate-specific antigen (PSA) progression (TTPP), radiographic progression-free survival (rPFS), overall survival (OS), prostate cancer-specific survival (PCSS), and safety. Outcomes were compared between patients with and without CCVDs (CCVD- vs CCVD+) and between treatment arms within each group.
RESULTS: The CCVD- group included 142 patients (75 ENZ and 67 ABI), and the CCVD+ group included 36 patients (14 ENZ and 22 ABI). The most frequent CCVD was cerebral infarction (n = 11, 31%). Survival outcomes did not differ significantly between patients in the CCVD- group and those in the CCVD+ group (median TTPP 15.2 vs 21.2; p = 0.8001; rPFS 18.1 vs 9.4; p = 0.0971; OS 37.4 vs 30.5; p = 0.1793; PCSS 46.8 vs 32.1; p = 0.6348). Within both groups, ENZ and ABI showed no significant differences in TTPP, rPFS, OS, or PCSS. Adverse event rates were also comparable across CCVD groups and treatment arms.
CONCLUSIONS: Patients with CCVDs showed no significant differences in survival or safety compared with those without CCVDs, and ENZ and ABI produced similar outcomes in both groups. These findings indicate that both agents remain feasible options irrespective of CCVD history.
PUBLIC TRIALS REGISTRY: The trial was registered with the University Hospital Medical Information Network (UMIN) Center under the identifier UMIN000015529 on November 1, 2014.
PMID:42840419 | PMC:PMC13639697 | DOI:10.31662/jmaj.2026-0201