Enzalutamide + androgen deprivation therapy (ADT) versus flutamide + ADT in Japanese men with castration-resistant prostate cancer: AFTERCAB study

Hiroji Uemura; Kazuki Kobayashi; Akira Yokomizo; Shiro Hinotsu; Shigeo Horie; Yoshiyuki Kakehi; Seiji Naito; Norio Nonomura; Osamu Ogawa; Mototsugu Oya; Kazuhiro Suzuki; Atsushi Saito; Satoshi Uno; Hideyuki Akaza

doi:10.1002/bco2.103

Enzalutamide + androgen deprivation therapy (ADT) versus flutamide + ADT in Japanese men with castration-resistant prostate cancer: AFTERCAB study

BJUI Compass. 2021 Aug 20;3(1):26-36. doi: 10.1002/bco2.103. eCollection 2022 Jan.

Authors

Hiroji Uemura¹, Kazuki Kobayashi², Akira Yokomizo³, Shiro Hinotsu⁴, Shigeo Horie⁵, Yoshiyuki Kakehi⁶, Seiji Naito³, Norio Nonomura⁷, Osamu Ogawa⁸, Mototsugu Oya⁹, Kazuhiro Suzuki¹⁰, Atsushi Saito¹¹, Satoshi Uno¹¹, Hideyuki Akaza¹²

Affiliations

¹ Yokohama City University Medical Center Yokohama Japan.
² Yokosuka Kyosai Hospital Yokosuka Japan.
³ Harasanshin Hospital Fukuoka Japan.
⁴ Sapporo Medical University Sapporo Japan.
⁵ Graduate School of Medicine Juntendo University Tokyo Japan.
⁶ Department of Urology National University Corporation Kagawa University Takamatsu Japan.
⁷ Graduate School of Medicine Osaka University Osaka Japan.
⁸ Graduate School of Medicine Kyoto University Kyoto Japan.
⁹ School of Medicine Keio University Tokyo Japan.
¹⁰ Graduate School of Medicine Gunma University Maebashi Japan.
¹¹ Astellas Pharma Inc. Tokyo Japan.
¹² Department of Strategic Investigation on Comprehensive Cancer Network, Research Center for Advanced Science and Technology The University of Tokyo Tokyo Japan.

Abstract

Objectives: The objective of the study is to compare the efficacy and safety of alternative androgen therapy (AAT) with enzalutamide + androgen deprivation therapy (ADT) and flutamide + ADT in the treatment of Japanese men with metastatic or nonmetastatic castration-resistant prostate cancer (CRPC) who progressed despite combined androgen blockade (CAB) with bicalutamide + ADT. AAT treatment sequence was also investigated.

Materials and methods: The open-label, Phase 4 AFTERCAB study (NCT02918968) was conducted from November 2016 to March 2020 in Japanese men aged ≥20 years with asymptomatic or mildly symptomatic CRPC. Patients were initially randomized to enzalutamide (160 mg/day) + ADT (enzalutamide first) or flutamide (375mg/day [125mg three times daily]) + ADT (flutamide first) as first-line therapy. Following prostate-specific antigen (PSA) progression, other disease progression, or discontinuation of first-line therapy due to an adverse event (AE), patients switched to the other treatment as second-line therapy. The primary endpoint was time to PSA progression with first-line therapy (TTPP1). Secondary endpoints included TTPP2 (TTPP1 + time to PSA progression with second-line therapy). AEs were monitored to assess safety.

Results: Overall, 206 men were randomized (enzalutamide first, n = 102; flutamide first, n = 104) and stratified by study site and disease stage; 133 patients transitioned to second-line therapy (enzalutamide first, n = 48; flutamide first, n = 85). TTPP1 was significantly improved with enzalutamide first versus flutamide first (median 21.4 months vs. 5.8 months; hazard ratio [HR] 0.42; 95% confidence interval [CI] [0.29, 0.61]). TTPP2 was numerically improved with enzalutamide first versus flutamide first (median not reached vs. 21.2 months; HR 0.76; 95% CI [0.48, 1.19]). Both treatments were generally well tolerated, with AEs consistent with their known safety profiles.

Conclusion: First-line AAT with enzalutamide + ADT provided a significant improvement in time to PSA progression versus flutamide + ADT. Enzalutamide + ADT may therefore be the preferred first-line AAT option in Japanese men with metastatic or nonmetastatic CRPC who progress despite CAB with bicalutamide + ADT.

Keywords: AFTERCAB; Japan; alternative androgen therapy; androgen deprivation therapy; bicalutamide; castration‐resistant prostate cancer; combined androgen blockade; enzalutamide; flutamide; prostate‐specific antigen progression.