Dose modification in enzalutamide and abiraterone plus prednisolone for castration-resistant prostate cancer: A subanalysis from the ENABLE study for PCa

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

doi:10.1002/pros.24796

Dose modification in enzalutamide and abiraterone plus prednisolone for castration-resistant prostate cancer: A subanalysis from the ENABLE study for PCa

Prostate. 2024 Sep 20. doi: 10.1002/pros.24796. Online ahead of print.

Authors

Nobumichi Tanaka¹, Kouji Izumi², Yasushi Nakai¹, Takashi Shima³, Yuki Kato^{2

4}, Koji Mita⁵, Manabu Kamiyama⁶, Shogo Inoue⁷, Seiji Hoshi⁸, Takehiko Okamura⁹, Yuko Yoshio¹⁰, Hideki Enokida¹¹, Ippei Chikazawa¹², Noriyasu Kawai¹³, Kohei Hashimoto¹⁴, Takashi Fukagai¹⁵, Kazuyoshi Shigehara^{2

16}, Shizuko Takahara^{17

18}, Atsushi Mizokami²

Affiliations

¹ Department of Urology and Department of Prostate Brachytherapy, Nara Medical University, Kashihara, Japan.
² Department of Integrative Cancer Therapy and Urology, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan.
³ Department of Urology, Toyama Prefectural Central Hospital, Toyama, Japan.
⁴ Department of Urology, Fukui-ken Saiseikai Hospital, Fukui, Japan.
⁵ Department of Urology, Hiroshima City North Medical Center Asa Citizens Hospital, Hiroshima, Japan.
⁶ Department of Urology, University of Yamanashi, Chuo, Japan.
⁷ Department of Urology, Shobara Red Cross Hospital, Shobara, Japan.
⁸ Department of Urology, Fukushima Medical University, Fukushima, Japan.
⁹ Department of Urology, Anjo Kosei Hospital, Anjo, Japan.
¹⁰ Mie University Graduate School of Medicine, Nephro-Urologic Surgery and Andrology, 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 School of Medicine, Shinagawa-ku, Japan.
¹⁶ Department of Urology, Ishikawa Prefectural Central Hospital, Kanazawa, Japan.
¹⁷ Innovative Clinical Research Center, Kanazawa University, Kanazawa, Japan.
¹⁸ Medical Research Support Center, University of Fukui Hospital, Fukui, Japan.

PMID: 39301921
DOI: 10.1002/pros.24796

Abstract

Background: A head-to-head comparison between enzalutamide (ENZ) and abiraterone plus prednisolone (ABI) revealed similar survival benefits for castration-resistant prostate cancer (CRPC) in the ENABLE study for PCa. Considering that a dose reduction of ENZ and ABI has demonstrated sufficient inhibitory ability of androgen receptor (AR) signaling, we analyzed the efficacy of modified doses of these agents in the ENABLE study for PCa.

Methods: This investigator-initiated, multicenter, randomized controlled trial that was conducted in Japan analyzed the prespecified survival endpoints, prostate-specific antigen (PSA) response rate ( ≥50% decline from baseline), and safety profile in patients treated with modified doses (ENZ ≤ 120 mg/day, ABI ≤ 750 mg/day) compared with those treated with a standard dose (ENZ 160 mg/day, ABI 1000 mg/day) as a starting dose.

Results: In total, 92 patients in each arm were treated and analyzed; 16 patients were treated with a modified dose in both the ENZ and ABI arms, respectively. Moreover, 32 patients treated with modified doses showed a significantly better time to PSA progression (TTPP) and overall survival (OS) compared with the 152 patients treated with a standard dose (HR 0.47, 95%CI 0.27-0.83, p = 0.0379, and HR 0.35, 95%CI 0.19-0.63, p = 0.0162). Despite a significantly longer TTPP in the modified ABI group than in the standard ABI group (HR 0.29, 95%CI 0.14-0.62, p = 0.0248), no significant difference was observed in the TTPP between the modified and standard ENZ groups (p = 0.5366). Furthermore, similar adverse event rates and grades were observed in each treatment dose group.

Conclusions: The modified doses of ABI showed better TTPP than the standard dose of ABI and may be a potential treatment option for CRPC patients; however, its mechanism is still unclear, although its ability to suppress AR signaling is equivalent to that of a standard dose.

Keywords: abiraterone; androgen‐deprivation therapy; castration‐resistant prostate cancer; dose modification; enzalutamide.

Grants and funding

The Japanese Foundation for Multidisciplinary Treatment of Cancer