Prognostic impact of dose reduction in androgen receptor pathway inhibitors for castration-resistant prostate cancer

Yamada, Shuhei; Shiota, Masaki; Blas, Leandro; Matsumoto, Takashi; Kashiwagi, Eiji; Takeuchi, Ario; Inokuchi, Junichi; Shiga, Kenichiro; Yokomizo, Akira; Eto, Masatoshi

doi:10.1016/j.prnil.2021.10.001

Cited by 8 publications

(7 citation statements)

References 27 publications

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“…Some reports showed that induction dose of ARSI correlates oncological outcome. (13)(14)(15) 17) Although induction dose correlates oncological outcome mentioned above, our cohort included both full (standard) dose and reduced dose induction cases. Therefor we reanalyzed full dose induction subgroups from our overall cohort to compare true difference of e cacy of ARSI against chemo-naïve CRPC in this study.…”

Section: Discussionmentioning

confidence: 99%

“…However, it was reported that reduced induction dose of ARSI correlated with reduced e cacy. (13)(14)(15) Therefore we need to compare full dose induction cohort to analyze the true difference of e cacy between abiraterone acetate and enzalutamide. In this study, we analyzed full dose induction subgroups in our overall cohort and investigated difference of e cacy between abiraterone acetate and enzalutamide.…”

Section: Introductionmentioning

confidence: 99%

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Abiraterone acetate versus enzalutamide against chemo-naïve castration resistant prostate cancer with full dose induction

Shimomura,

Mori,

Yasue

et al. 2024

Preprint

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Purpose We recently released the multi-institutional real-world analysis about the difference of survival outcome between abiraterone acetate and enzalutamide against chemo-naïve castration resistant prostate cancer as first line setting. Although reduced dose induction cases were included in that analysis, induction dose reduction might correlate reduced efficacy. In this study, we analyzed full dose induction subgroups from our overall cohort and investigated true difference of efficacy between these agents.Methods A total of 220 chemotherapy-naïve CRPC cases treated with full dose induction of first-line ARSI were analyzed. Outcome measures were PSA response, PSA progression-free survival (PSA-PFS), treatment failure free survival (TFF), cancer specific survival (CSS) and overall survival (OS).Results Abiraterone acetate (A) and enzalutamide (E) were administered to 58 and 162 patients, respectively. The median PSA response rate (− 65.4% [A] and − 81.5% [E], p = 0.0252), PSA decline ≥ 90% (22.4% [A] and 37.0% [E], p = 0.0478), PSA-PFS (median 4 months [A] and 7 months [E], p = 0.00833), TFF (median 6 months [A] and 15 months [E], p < 0.0001), CSS (median 45 months [A] and not reached [E], p < 0.0001) and OS (median 34 months [A] and 80 months [E], p < 0.001) were significantly better in the enzalutamide group.Conclusion This study showed that PSA response, PSA-PFS, TTF, CSS and OS were better with first-line enzalutamide administration. Direct inhibition of androgen receptor signaling by enzalutamide is associated with better clinical outcomes in full dose induction cohort.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Abiraterone acetate versus enzalutamide against chemo-naïve castration resistant prostate cancer with full dose induction

Shimomura,

Mori,

Yasue

et al. 2024

Preprint

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“…Although several new treatments have been recently approved, the oncological outcomes of patients with CRPC are still suboptimal. 3 , 4 , 23 In addition, CRPC patients with AR-V7 showed poorer oncological outcomes after treatment with next-generation hormonal therapy than patients without AR-V7. 11 , 24 Despite drug-induced toxicities, taxane-based chemotherapy should be considered in CRPC patients with AR-V7 25 because AR-V7-expressing tumors were found to be sensitive to taxane-based chemotherapeutic agents.…”

Section: Discussionmentioning

confidence: 99%

“… 1 , 2 Despite treatment with recently developed hormonal agents, the median survival of patients with castration-resistant prostate cancer (CRPC) has been reported to be less than 2 years. 2 , 3 , 4 Although multiple mechanisms have been shown to contribute to CRPC progression, AR splice variants (AR-Vs) are considered one of the most important mechanisms, 5 , 6 , 7 , 8 with one of these variants, AR-V7, considered a treatment selection biomarker in patients with CRPC. 7 , 9 , 10 Because CRPC patients with AR-V7 showed unfavorable oncological outcomes after treatment with next-generation hormonal agents, 11 , 12 novel drugs are still needed for treatment of patients with CRPC, particularly those with AR-V7.…”

Section: Introductionmentioning

confidence: 99%

A novel biguanide derivative, IM176, induces prostate cancer cell death by modulating the AMPK-mTOR and androgen receptor signaling pathways

Kim

Yoo

Lim

et al. 2023

Prostate International

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“…Several studies have reported that this factor had no effect on the time to enzalutamide discontinuation or PSA progression ( Terada et al, 2016 ; Vinh-Hung et al, 2020 ; Miura et al, 2021 ; Tsuzuki et al, 2021 ). On contrary, one retrospective study suggested inferior oncological outcomes when treated with reduced-dose androgen receptor pathway inhibitors for CRPC ( Yamada et al, 2022 ). The study also suggested that full-dose administration of those medications for CRPC may be appropriate if feasible.…”

Section: Discussionmentioning

confidence: 99%

Pharmacist-Urologist Collaborative Management Improves Clinical Outcomes in Patients With Castration-Resistant Prostate Cancer Receiving Enzalutamide

et al. 2022

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Background: Enzalutamide is useful for the treatment of castration-resistant prostate cancer (CRPC). Despite its usefulness, adverse events (AEs) sometimes force patients to discontinue treatment. To maximize patient care, we developed an ambulatory care pharmacy practice that allows collaboration between a pharmacist and urologist to manage patients with CRPC receiving enzalutamide. In this study, we investigated the efficacy of this collaborative management.Methods: A retrospective chart review of 103 patients with CRPC receiving enzalutamide in our hospital between May 2014 and December 2020 was performed. Our collaborative management was implemented in October 2016. Before being examined by urologists, patients visited the oncology pharmacy consultation room for a face-to-face consultation, wherein the oncology pharmacists assessed factors such as adherence to enzalutamide, any AEs and their grades, and provided their suggestions to the urologists. The time to enzalutamide discontinuation and prostate-specific antigen progression were compared between patients who started enzalutamide before (n = 41) and after (n = 62) the implementation of the collaborative management. A multivariate Cox regression analysis was performed to analyze the factors associated with enzalutamide discontinuation.Results: After implementing collaborative management, the pharmacists had 881 patient consultations. Among the 476 suggestions from pharmacists, 345 were accepted by urologists. The most frequent suggestion was supportive care in enzalutamide treatment (224 suggestions). Multivariate analysis showed that collaborative management [hazard ratio (HR) 0.53, 95% confidence interval (CI) 0.31–0.89, p = 0.017] and higher prostate-specific antigen (PSA; HR 2.41, 95% CI 1.36–4.28, p = 0.003) were significantly associated with enzalutamide discontinuation. The median time to discontinuation (18.9 vs. 7.6 months, p = 0.012), time to discontinuation due to AEs (not reached in both groups, p = 0.001), and time to PSA progression (13.3 vs. 5.8 months, p = 0.002) were all significantly longer in the after group.Conclusions: We implemented a pharmacist-urologist collaborative management program for outpatients with CRPC receiving enzalutamide. The results revealed that collaborative management was useful for prolonging the time to enzalutamide discontinuation.

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Prognostic impact of dose reduction in androgen receptor pathway inhibitors for castration-resistant prostate cancer

Cited by 8 publications

References 27 publications

Abiraterone acetate versus enzalutamide against chemo-naïve castration resistant prostate cancer with full dose induction

Abiraterone acetate versus enzalutamide against chemo-naïve castration resistant prostate cancer with full dose induction

A novel biguanide derivative, IM176, induces prostate cancer cell death by modulating the AMPK-mTOR and androgen receptor signaling pathways

Pharmacist-Urologist Collaborative Management Improves Clinical Outcomes in Patients With Castration-Resistant Prostate Cancer Receiving Enzalutamide

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