Mehmet A Bilen, Sabree Burbage, Carmine Rossi, Ibrahim Khilfeh, Lilian Diaz, Yuxi Wang, Dominic Pilon, Gordon Brown, Neal Shore, Benjamin Lowentritt, Daniel W Lin
{"title":"brca1 /2阳性和同源重组修复阴性转移性去势敏感前列腺癌患者真实世界预后的比较","authors":"Mehmet A Bilen, Sabree Burbage, Carmine Rossi, Ibrahim Khilfeh, Lilian Diaz, Yuxi Wang, Dominic Pilon, Gordon Brown, Neal Shore, Benjamin Lowentritt, Daniel W Lin","doi":"10.1007/s12325-025-03270-z","DOIUrl":null,"url":null,"abstract":"<p><strong>Introduction: </strong>This real-world study compared time-to-next-treatment (TTNT), time-to-castration resistance (TTCR), and overall survival between patients with BRCA1/2-positive (BRCA+) and homologous recombination repair-negative (HRR-) metastatic castration-sensitive prostate cancer (mCSPC).</p><p><strong>Methods: </strong>Patients who received a genetic test and initiated treatment for mCSPC (index date) after 1/1/2018 were selected from the Flatiron Health-Foundation Medicine, Inc. Metastatic PC Clinico-Genomic Database (1/1/2017-12/31/2022). Outcomes were compared between patients with ≥ 1 positive BRCA test (BRCA+) and those without detected HRR mutations (HRR-) using weighted Kaplan-Meier analyses and Cox proportional hazards models after baseline characteristics (12 months pre-index) were balanced using inverse-probability of treatment weighting.</p><p><strong>Results: </strong>In total, 149 patients with BRCA+ and 1066 with HRR- mCSPC were included. Baseline characteristics were well-balanced after weighting. By 24 months after treatment initiation, a significantly higher proportion of the BRCA+ than the HRR- cohort progressed to next treatment [69.7% vs. 56.8%; hazard ratio (HR) = 1.45 (95% confidence interval (CI) 1.10, 1.92), p = 0.009]; median TTNT was shorter in the BRCA+ than the HRR- cohort (10.9 vs. 18.7 months). By 24 months, a significantly higher proportion of the BRCA+ than the HRR- cohort progressed to castration resistance [72.2% vs. 61.4%; HR = 1.46 (95% CI 1.16, 1.84), p = 0.001]; median TTCR was shorter in the BRCA+ than HRR- cohort (12.9 vs. 16.9 months). Numerically fewer patients in the BRCA+ than the HRR- cohort survived 24 months after PC diagnosis [80.6% vs. 85.4%; HR = 1.46 (95% CI 0.99, 2.14), p = 0.054].</p><p><strong>Conclusion: </strong>Findings demonstrate worse outcomes for patients with BRCA+ mCSPC treated with available advanced therapies, supporting the need for effective genetically targeted therapies in this population.</p>","PeriodicalId":7482,"journal":{"name":"Advances in Therapy","volume":" ","pages":""},"PeriodicalIF":3.4000,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Comparison of Real-World Outcomes between Patients with BRCA1/2-Positive and Homologous Recombination Repair-Negative Metastatic Castration-Sensitive Prostate Cancer.\",\"authors\":\"Mehmet A Bilen, Sabree Burbage, Carmine Rossi, Ibrahim Khilfeh, Lilian Diaz, Yuxi Wang, Dominic Pilon, Gordon Brown, Neal Shore, Benjamin Lowentritt, Daniel W Lin\",\"doi\":\"10.1007/s12325-025-03270-z\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Introduction: </strong>This real-world study compared time-to-next-treatment (TTNT), time-to-castration resistance (TTCR), and overall survival between patients with BRCA1/2-positive (BRCA+) and homologous recombination repair-negative (HRR-) metastatic castration-sensitive prostate cancer (mCSPC).</p><p><strong>Methods: </strong>Patients who received a genetic test and initiated treatment for mCSPC (index date) after 1/1/2018 were selected from the Flatiron Health-Foundation Medicine, Inc. Metastatic PC Clinico-Genomic Database (1/1/2017-12/31/2022). Outcomes were compared between patients with ≥ 1 positive BRCA test (BRCA+) and those without detected HRR mutations (HRR-) using weighted Kaplan-Meier analyses and Cox proportional hazards models after baseline characteristics (12 months pre-index) were balanced using inverse-probability of treatment weighting.</p><p><strong>Results: </strong>In total, 149 patients with BRCA+ and 1066 with HRR- mCSPC were included. Baseline characteristics were well-balanced after weighting. By 24 months after treatment initiation, a significantly higher proportion of the BRCA+ than the HRR- cohort progressed to next treatment [69.7% vs. 56.8%; hazard ratio (HR) = 1.45 (95% confidence interval (CI) 1.10, 1.92), p = 0.009]; median TTNT was shorter in the BRCA+ than the HRR- cohort (10.9 vs. 18.7 months). 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引用次数: 0
摘要
这项现实世界的研究比较了brca1 /2阳性（BRCA+）和同源重组修复阴性（HRR-）转移性去势敏感前列腺癌（mCSPC）患者的下一次治疗时间（TTNT）、去势抵抗时间（TTCR）和总生存率。方法：选择2018年1月1日之后在Flatiron Health-Foundation Medicine， Inc.接受基因检测并开始治疗mCSPC（指标日期）的患者。转移性PC临床基因组数据库（1/1/2017-12/31/2022）。采用加权Kaplan-Meier分析和Cox比例风险模型，比较BRCA检测≥1阳性（BRCA+）和未检测到HRR突变（HRR-）的患者在基线特征（指数前12个月）采用反概率治疗加权平衡后的结果。结果：共纳入149例BRCA+患者和1066例HRR- mCSPC患者。加权后基线特征平衡良好。在开始治疗24个月后，BRCA+的比例明显高于HRR-队列进展到下一次治疗的比例[69.7% vs. 56.8%；风险比（HR) = 1.45(95%可信区间（CI） 1.10, 1.92), p = 0.009）；BRCA+组的中位TTNT短于HRR-组（10.9个月vs 18.7个月）。到24个月时，BRCA+组进展为去势抵抗的比例明显高于HRR-组[72.2% vs. 61.4%；HR = 1.46 (95% CI 1.16, 1.84), p = 0.001]；BRCA+组的中位TTCR短于HRR-组（12.9个月vs 16.9个月）。BRCA+组患者在PC诊断后24个月的存活率低于HRR-组[80.6% vs. 85.4%；HR = 1.46 (95% CI 0.99, 2.14), p = 0.054)。结论：研究结果表明，BRCA+ mCSPC患者接受现有先进疗法治疗的结果更差，支持对这一人群进行有效的基因靶向治疗的需求。
Comparison of Real-World Outcomes between Patients with BRCA1/2-Positive and Homologous Recombination Repair-Negative Metastatic Castration-Sensitive Prostate Cancer.
Introduction: This real-world study compared time-to-next-treatment (TTNT), time-to-castration resistance (TTCR), and overall survival between patients with BRCA1/2-positive (BRCA+) and homologous recombination repair-negative (HRR-) metastatic castration-sensitive prostate cancer (mCSPC).
Methods: Patients who received a genetic test and initiated treatment for mCSPC (index date) after 1/1/2018 were selected from the Flatiron Health-Foundation Medicine, Inc. Metastatic PC Clinico-Genomic Database (1/1/2017-12/31/2022). Outcomes were compared between patients with ≥ 1 positive BRCA test (BRCA+) and those without detected HRR mutations (HRR-) using weighted Kaplan-Meier analyses and Cox proportional hazards models after baseline characteristics (12 months pre-index) were balanced using inverse-probability of treatment weighting.
Results: In total, 149 patients with BRCA+ and 1066 with HRR- mCSPC were included. Baseline characteristics were well-balanced after weighting. By 24 months after treatment initiation, a significantly higher proportion of the BRCA+ than the HRR- cohort progressed to next treatment [69.7% vs. 56.8%; hazard ratio (HR) = 1.45 (95% confidence interval (CI) 1.10, 1.92), p = 0.009]; median TTNT was shorter in the BRCA+ than the HRR- cohort (10.9 vs. 18.7 months). By 24 months, a significantly higher proportion of the BRCA+ than the HRR- cohort progressed to castration resistance [72.2% vs. 61.4%; HR = 1.46 (95% CI 1.16, 1.84), p = 0.001]; median TTCR was shorter in the BRCA+ than HRR- cohort (12.9 vs. 16.9 months). Numerically fewer patients in the BRCA+ than the HRR- cohort survived 24 months after PC diagnosis [80.6% vs. 85.4%; HR = 1.46 (95% CI 0.99, 2.14), p = 0.054].
Conclusion: Findings demonstrate worse outcomes for patients with BRCA+ mCSPC treated with available advanced therapies, supporting the need for effective genetically targeted therapies in this population.
期刊介绍：
Advances in Therapy is an international, peer reviewed, rapid-publication (peer review in 2 weeks, published 3–4 weeks from acceptance) journal dedicated to the publication of high-quality clinical (all phases), observational, real-world, and health outcomes research around the discovery, development, and use of therapeutics and interventions (including devices) across all therapeutic areas. Studies relating to diagnostics and diagnosis, pharmacoeconomics, public health, epidemiology, quality of life, and patient care, management, and education are also encouraged.
The journal is of interest to a broad audience of healthcare professionals and publishes original research, reviews, communications and letters. The journal is read by a global audience and receives submissions from all over the world. Advances in Therapy will consider all scientifically sound research be it positive, confirmatory or negative data. Submissions are welcomed whether they relate to an international and/or a country-specific audience, something that is crucially important when researchers are trying to target more specific patient populations. This inclusive approach allows the journal to assist in the dissemination of all scientifically and ethically sound research.
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