Efficacy and Safety of Enzalutamide and Abiraterone Plus Prednisolone in Elder Castration‐Resistant Prostate Cancer Patients: A Sub‐Analysis From the ENABLE Study

ABSTRACT Background Clinical trials rarely focus on elder patients with castration‐resistant prostate cancer (CRPC), and data on the outcomes of second‐generation androgen receptor signaling inhibitors (ARSIs) remain limited. Methods The ENABLE study for prostate cancer was an investigator‐initiated, multicenter, randomized controlled trial conducted in Japan to compare enzalutamide (ENZ) and abiraterone plus prednisolone (ABI). This sub‐analysis was performed to evaluate the efficacy and the safety profiles between patients aged ≥ 75 (older) and < 75 years (younger), and then between the ENZ and ABI arms in the older and the younger cohort separately. Results The ENZ arm included 41 younger and 51 older patients, while the ABI arm included 36 younger and 56 older patients. No significant differences in survival endpoints were observed between younger and older patients. Median time to prostate‐specific antigen (PSA) progression (TTPP) was 15.2 months for younger and 21.2 months for older patients (HR 0.84, 95% CI 0.53–1.33, p  = 0.4647). Median overall survival (OS) was 33.7 months for younger and 37.8 months for older patients (HR 0.80, 95% CI 0.50–1.29, p  = 0.3651). Among older patients ( n  = 107), the ENZ arm had a TTPP of 21.2 months compared to 10.1 months for the ABI arm and an OS of 37.8 months compared to 44.7 months for the ABI arm ( p  = 0.1506 and p  = 0.9321, respectively). Any grade and grade ≥ 3 adverse events were observed in 47 (61%) and 11 (14%) younger patients and 73 (68%) and 18 (17%) older patients, respectively. No significant differences were found in any grade or grade ≥ 3 adverse events between younger and older patients ( p  = 0.3487 and p  = 0.6885, respectively). Conclusions ARSIs demonstrated similar efficacy and safety in both younger and older patients. ENZ may be a more suitable option for older patients due to its higher PSA response rate. Clinical Trial Registration This trial was registered with the University Hospital Medical Information Network (UMIN) Center under identifier UMIN000015529.