Enzalutamide Versus Abiraterone plus Prednisolone Before Chemotherapy for Castration-resistant Prostate Cancer: A Multicenter Randomized Controlled Trial

• Published in: European urology open science (Online) 2022-07, Vol.41, p.16-23
• Main Authors: Izumi, Kouji, Shima, Takashi, Mita, Koji, Kato, Yuki, Kamiyama, Manabu, Inoue, Shogo, Tanaka, Nobumichi, Hoshi, Seiji, Okamura, Takehiko, Yoshio, Yuko, Enokida, Hideki, Chikazawa, Ippei, Kawai, Noriyasu, Hashimoto, Kohei, Fukagai, Takashi, Shigehara, Kazuyoshi, Takahara, Shizuko, Kadono, Yoshifumi, Mizokami, Atsushi
• Format: Article
• Language: English
• Subjects: Abiraterone; Androgen deprivation therapy; Androgen receptor signaling–targeted therapy; Castration-resistant prostate cancer; Endocrine therapy; Enzalutamide; Prostate Cancer; Randomized controlled trial
• ISSN: 2666-1683; 2666-1691; 2666-1683
• DOI: 10.1016/j.euros.2022.04.016

Enzalutamide (ENZ) and abiraterone plus prednisolone (ABI) improve survival in castration-resistant prostate cancer (CRPC). However, which agent is better for CRPC patients remains unclear. The enzalutamide versus abiraterone plus prednisolone before chemotherapy for castration-resistant prostate cancer study (ENABLE study for PCa) is a head-to-head comparison between ENZ and ABI in this population. ENZ did not show any further survival benefit in comparison to ABI, but showed a better prostate-specific antigen response rate with a low rate of severe adverse events, suggesting that use of ENZ before ABI has potential clinical benefits in CRPC. Enzalutamide (ENZ) and abiraterone plus prednisolone (ABI) improve survival in castration-resistant prostate cancer (CRPC). However, which agent is better for patients with CRPC remains unclear. To evaluate whether ENZ or ABI is better as first-line treatment for CRPC. An investigator-initiated, multicenter, randomized controlled trial was conducted in Japan. The study enrolled 203 patients with CRPC before chemotherapy between February 20, 2015, and July 31, 2019. Patients were randomly assigned 1:1 to the ENZ or ABI arm. The primary endpoint was time to prostate-specific antigen (PSA) progression. Secondary endpoints included the PSA response rate (≥50% decline from baseline), overall survival, and safety. A log-rank test was used for comparison of survival analyses between arms. After randomization, 92 patients in each arm were treated and analyzed. Time to PSA progression did not significantly differ between the arms (median 21.2 mo for ENZ and 11.9 mo for ABI; hazard ratio [HR] 0.81, 95% confidence interval [CI] 0.51–1.27; p = 0.1732). There was a significant difference in the PSA response rate between the arms (72% for ENZ and 57% for ABI; p = 0.0425). There was no significant difference in overall survival (median 32.9 mo for ENZA and 35.5 mo for ABI; HR 1.17, 95% CI 0.72–1.88; p = 0.5290). Grade ≥3 adverse events were observed in 11% of patients in the ENZA arm and 21% in the ABI arm (p = 0.1044). ENZ did not show any survival benefit in comparison to ABI, but showed a better PSA response rate with a low rate of severe adverse events in CRPC. Results from our study suggest that use of enzalutamide before abiraterone may have potential clinical benefits for patients with castration-resistant prostate cancer.