<scp>Real‑world</scp> survival outcome comparing abiraterone acetate plus prednisone and enzalutamide for <scp>nonmetastatic castration‐resistant</scp> prostate cancer

Tsujino, Takuya; Tokushige, Satoshi; Komura, Kazumasa; Fukuokaya, Wataru; Adachi, Takahiro; Hirasawa, Yosuke; Hashimoto, Takeshi; Yoshizawa, Atsuhiko; Saruta, Masanobu; Ohno, Takaya; Nakamori, Keita; Maenosono, Ryoichi; Nishimura, Kazuki; Yamazaki, Shogo; Uchimoto, Taizo; Yanagisawa, Takafumi; Mori, Keiichiro; Urabe, Fumihiko; Tsuzuki, Shunsuke; Iwatani, Kosuke; Yamamoto, Shutaro; Takahara, Kiyoshi; Inamoto, Teruo; Kimura, Takahiro; Ohno, Yoshio; Shiroki, Ryoichi; Azuma, Haruhito

doi:10.1002/cam4.6536

Cited by 2 publications

References 30 publications

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Comparison of abiraterone, enzalutamide, and apalutamide for metastatic hormone‐sensitive prostate cancer: A multicenter study

Yanagisawa,

Fukuokaya,

Hatakeyama

et al. 2024

The Prostate

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PurposeWe aimed to assess the differential efficacy and safety of androgen receptor pathway inhibitors (ARPI), such as abiraterone, enzalutamide, and apalutamide, in patients with metastatic hormone‐sensitive prostate cancer (mHSPC) in a real‐world practice setting.MethodsWe retrospectively reviewed the records of consequent 668 patients with mHSPC treated with ARPI plus androgen deprivation therapy between September 2015 and December 2023. Based on the LATITUDE criteria, the comparison among abiraterone, enzalutamide, and apalutamide was exclusively conducted in high‐risk patients. Prostate‐specific antigen (PSA) responses such as the achievement of 95% and 99% PSA decline, overall survival (OS), cancer‐specific survival (CSS), time to castration‐resistant prostate cancer (CRPC), and the incidence of adverse events (AEs) were compared. All two‐group comparisons relied on propensity score matching (PSM) to minimize the effect on possible confounders.ResultsIn total, 297 patients with high‐risk mHSPC treated with abiraterone, 127 with enzalutamide, and 142 with apalutamide were compared. There were no differences in time to CRPC (p = 0.13), OS (p = 0.7), and CSS (p = 0.5) among the three ARPIs. No differences were observed in the achievement rates for 95% PSA decline at 3 months among the three ARPIs, while abiraterone was significantly better in 99% PSA decline achievement compared to apalutamide (72% vs. 57%, p = 0.003). The aforementioned oncologic outcomes were sustained even when performing PSM analyzes. Although skin rash for APA (34%) was the highest incidence of AEs, there were no differences in the rates of severe AEs across the three ARPIs. Enzalutamide resulted in the lowest treatment discontinuation rates (10%) other than disease progression compared to the other regimens.ConclusionsAbiraterone, enzalutamide, and apalutamide have comparable oncologic outcomes in terms of OS, CSS, and time to CRPC in patients with high‐risk mHSPC. Our data on differential treatment discontinuation rates, PSA response, and AE profiles can help guide clinical decision‐making.

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Comparison of abiraterone, enzalutamide, and apalutamide for metastatic hormone‐sensitive prostate cancer: A multicenter study

Yanagisawa,

Fukuokaya,

Hatakeyama

et al. 2024

The Prostate

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CYP3A5 inhibition causes G1/S blockade and synergizes with CDK4/6 inhibitor to suppress prostate cancer cell growth: Implications in reducing health disparity

Sharma,

Mohammed,

Tillett

et al. 2024

Preprint

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Prostate cancer (PC) is a leading cause of death in men because of the high incidence and long-term inefficacy of the existing treatment options. Furthermore, it exhibits significant health disparities that affect African-American (AA) men more adversely than others do. Previously, we established CYP3A5, a highly expressed protein in AAs PC, as a positive regulator of androgen receptor (AR) signaling. We examined the impact of CYP3A5 depletion on genome-wide transcriptional output using RNA sequencing to gain deeper mechanistic insights. The data revealed that 561 genes were downregulated and 263 were upregulated upon silencing of CYP3A5 in PC cells. Furthermore, in silico pathway analyses of differentially expressed genes suggested that the cell cycle regulation pathway was most significantly affected by CYP3A5 inhibition. Cell cycle analysis of CYP3A5-silenced cells and those treated with clobetasol, a specific CYP3A5 pharmacological inhibitor, showed G1/S phase blockade. Both CYP3A5-depletion and pharmacological inhibition resulted in the downregulation of cyclin D, cyclin B, and CDK2, along with the upregulation of p27kip1 but had minimal effects on CDK4/6 levels. Combination treatment with clobetasol and the CDK4/6 inhibitor palbociclib exhibited synergy with combination index (CI) values ranging from 0.28-0.78. Our findings support the utility of CYP3A5 as a druggable therapeutic target that works more effectively in combination with CDK4/6 inhibition to limit the progression of PC, especially for AA patients with AA. This combination addresses CDK4/6 inhibitor resistance, which is often linked to CDK2 overexpression, and can potentially be useful in reducing disparities in the clinical outcomes of PC.

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Real‑world survival outcome comparing abiraterone acetate plus prednisone and enzalutamide for nonmetastatic castration‐resistant prostate cancer

Cited by 2 publications

References 30 publications

Comparison of abiraterone, enzalutamide, and apalutamide for metastatic hormone‐sensitive prostate cancer: A multicenter study

Comparison of abiraterone, enzalutamide, and apalutamide for metastatic hormone‐sensitive prostate cancer: A multicenter study

CYP3A5 inhibition causes G1/S blockade and synergizes with CDK4/6 inhibitor to suppress prostate cancer cell growth: Implications in reducing health disparity

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