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

Kouji Izumi; Takashi Shima; Koji Mita; Yuki Kato; Manabu Kamiyama; Shogo Inoue; Nobumichi Tanaka; Seiji Hoshi; Takehiko Okamura; Yuko Yoshio; Hideki Enokida; Ippei Chikazawa; Noriyasu Kawai; Kohei Hashimoto; Takashi Fukagai; Kazuyoshi Shigehara; Shizuko Takahara; Yoshifumi Kadono; Atsushi Mizokami

doi:10.1016/j.euros.2022.04.016

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

Eur Urol Open Sci. 2022 May 19:41:16-23. doi: 10.1016/j.euros.2022.04.016. eCollection 2022 Jul.

Authors

Kouji Izumi¹, Takashi Shima², Koji Mita³, Yuki Kato^{1

4}, Manabu Kamiyama⁵, Shogo Inoue⁶, Nobumichi Tanaka⁷, Seiji Hoshi⁸, Takehiko Okamura⁹, Yuko Yoshio¹⁰, Hideki Enokida¹¹, Ippei Chikazawa¹², Noriyasu Kawai¹³, Kohei Hashimoto¹⁴, Takashi Fukagai¹⁵, Kazuyoshi Shigehara^{1

16}, Shizuko Takahara¹⁷, Yoshifumi Kadono¹, Atsushi Mizokami¹

Affiliations

¹ Department of Integrative Cancer Therapy and Urology, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan.
² Department of Urology, Toyama Prefectural Central Hospital, Toyama, Japan.
³ Department of Urology, Hiroshima City Asa Citizens Hospital, Horoshima, Japan.
⁴ Department of Urology, Fukui-ken Saiseikai Hospital, Fukui, Japan.
⁵ Department of Urology, University of Yamanashi, Yamanashi, Japan.
⁶ Department of Urology, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
⁷ Department of Urology, Nara Medical University, Nara, Japan.
⁸ Department of Urology, Fukushima Medical University, Fukushima, Japan.
⁹ Department of Urology, Anjo Kosei Hospital, Anjo, Japan.
¹⁰ Nephro-Urologic Surgery and Andrology, Mie University Graduate School of Medicine, Tsu, Japan.
¹¹ Department of Urology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan.
¹² Department of Urology, Kanazawa Medical University, Kahoku, Japan.
¹³ Department of Nephro-urology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
¹⁴ Department of Urology, School of Medicine, Sapporo Medical University, Sapporo, Japan.
¹⁵ Department of Urology, Showa University Koto Toyosu Hospital, Tokyo, Japan.
¹⁶ Department of Urology, Ishikawa Prefectural Central Hospital, Kanazawa, Japan.
¹⁷ Innovative Clinical Research Center, Kanazawa University, Kanazawa, Japan.

Abstract

Background: 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.

Objective: To evaluate whether ENZ or ABI is better as first-line treatment for CRPC.

Design setting and participants: 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.

Outcome measurements and statistical analysis: 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.

Results and limitations: 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).

Conclusions: 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.

Patient summary: Results from our study suggest that use of enzalutamide before abiraterone may have potential clinical benefits for patients with castration-resistant prostate cancer.

Keywords: Abiraterone; Androgen deprivation therapy; Androgen receptor signaling–targeted therapy; Castration-resistant prostate cancer; Endocrine therapy; Enzalutamide; Randomized controlled trial.