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Purpose We recently released the multi-institutional real-world analysis about the difference in survival outcomes between abiraterone acetate and enzalutamide against chemo-naïve castration-resistant prostate cancer (CRPC) in a first-line setting. Although reduced dose induction cases were included in that analysis, induction dose reduction might correlate with reduced efficacy. In this study, we analyzed full-dose induction subgroups from our overall cohort and investigated the true difference in efficacy between these agents. Methods A total of 220 chemotherapy-naïve CRPC cases treated with full-dose induction of first-line androgen receptor signaling inhibitor (ARSI) were analyzed. Outcome measures were prostate-specific antigen (PSA) response, PSA progression-free survival (PSA-PFS), treatment failure-free survival (TFF), cancer-specific survival (CSS), and overall survival (OS). Results Abiraterone acetate and enzalutamide 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 four months (A) and seven months (E), p = 0.00833), TFF (median six 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 E 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 the full-dose induction cohort.

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PURPOSE: Although docetaxel and ARSI are picked up as treatment options against chemo-naïve metastatic CRPC in clinical guidelines for prostate cancer, there is no clear evidence which agent should be introduced as first line treatment. Therefore, we investigated our CRPC cohort treated with docetaxel or ARSI as first-line agent against chemo-naïve CRPC to solve these clinical questions. PATIENTS AND METHODS: A total of 345 chemotherapy-naïve CRPC patients introduced to first-line docetaxel or ARSI (abiraterone or enzalutamide) between March 2006 and April 2017 at Jikei University Hospital and its affiliated institutions were included in this study. Propensity score matching method was used to minimize the patients' background. The outcome measures were PSA response rate, PSA decline ≥ 90%, cancer specific survival (CSS) and overall survival (OS). RESULTS: PSA decline correlated OS and CSS (p = 0.027, < 0.001, respectively) and median PSA decline rate was 60.4% in docetaxel group and 85.7% in ARSI group (p = 0.0311). Median OS was 33 m (95%CI: 27-53) in docetaxel group and 61 m (95%CI: 47-NA) in ARSI group (p = 0.0246). Median CSS was 34 m (95%CI: 27-53) in docetaxel group and NR (not reached) (95%CI: 61-NA) in ARSI group (p = 0.000133) in propensity score matching cohort. In multivariate analysis, ARSI induction first showed significantly better for OS and CSS (p = 0.0033 and < 0.001, respectively). CONCLUSION: In this study, better survival outcome with ARSI induction first than docetaxel against chemo-naïve CRPC. And the candidates who had survival benefit by induction docetaxel first could not be found in this study.

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PURPOSE: The androgen receptor axis-targeted (ARAT) agents abiraterone and enzalutamide have been introduced against castration-resistant prostate cancer (CRPC). However, determining which of these agents should be used first is a clinical challenge. Therefore, in this study, we compared the efficacy of first-line abiraterone and enzalutamide treatments in chemotherapy-naïve patients with CRPC. METHODS: A total of 242 chemotherapy-naïve CRPC cases treated with first-line ARAT were analyzed. Outcome measures were PSA response, PSA progression-free survival (PSA-PFS), time to treatment failure (TTF), cancer specific survival (CSS), and overall survival (OS). RESULTS: Abiraterone (A) and enzalutamide (E) were administered to 61 and 181 patients, respectively. The median PSA response rate (- 65.4% [A] and - 78.8% [E], p = 0.0341), PSA decline ≥ 30% (55.7% [A] and 72.9% [E], p = 0.0183), PSA-PFS (median 4 months [A] and 8 months [E], p = 0.0126), TTF (median 6 months [A] and 14 months [E], p < 0.0001), CSS (median 45 months [A] and not reached [E], p < 0.0001), and OS (median 28 months [A] and 80 months [E], p < 0.001) were significantly better in the enzalutamide group. In the multivariate analyses for CSS and OS, ALP (p = 0.00376) and ARAT (p < 0.001) (CSS), evidence of metastasis (p = 0.0467), Hb (p = 0.00205), and ARAT (p = 0.00514) (OS) were significant factors, respectively. 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.

Asunto(s)

Benzamidas , Neoplasias de la Próstata Resistentes a la Castración , Receptores Androgénicos , Masculino , Humanos , Neoplasias de la Próstata Resistentes a la Castración/patología , Antígeno Prostático Específico , Feniltiohidantoína/uso terapéutico , Nitrilos , Resultado del Tratamiento

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Nearly one third of men will incur biochemical recurrence after treatment for localized prostate cancer. Androgen deprivation therapy (ADT) is the therapeutic mainstay; however, some patients will transition to a castrate resistant state (castrate resistant prostate cancer, CRPC). Subjects with CRPC may develop symptomatic metastatic disease (mCRPC) and incur mortality several years later. Prior to metastatic disease, however, men acquire non-metastatic CRPC (nmCRPC) which lends the unique opportunity for intervention to delay disease progression and symptoms. This review addresses current therapies for nmCRPC, as well as novel therapeutics and pathway strategies targeting men with nmCRPC.

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Non-metastatic castration-resistant prostate cancer (nmCRPC) is a heterogeneous disease with variable potential in developing into overt metastases. It is an area of increased unmet need in advanced prostate cancer and for which there had been no great treatments until recent US Food and Drug Administration (FDA) approval of 2 novel anti-androgens apalutamide and enzalutamide, which were both approved given benefit in metastasis-free survival. Early data on the use of darolutamide, another novel anti-androgen, are also explored. This review discusses the pivotal trials that led to the approval of apalutamide and enzalutamide in the nmCRPC setting and discusses the key promises and challenges with the use of these agents.