Micah Ostrowski, Yeonjung Jo, Chadi Hage Chehade, Zeynep Irem Ozay, Georges Gebrael, Nicolas Sayegh, Edwin Lin, Ayana Srivastava, Abigail Gordhamer, Richard Ji, Haoran Li, Vinay Mathew Thomas, Sumati Gupta, Irbaz Bin Riaz, Benjamin L Maughan, Soumyajit Roy, Neeraj Agarwal, Umang Swami
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However, data are limited regarding the uptake of PARP inhibitors in these patients.</p><p><strong>Objective: </strong>To investigate the use of PARP inhibitors in patients with mCRPC harboring BRCA1/2 alterations.</p><p><strong>Design, setting, and participants: </strong>This retrospective cohort study used the deidentified Flatiron-Health electronic health record-derived database of US community and academic practices to extract patient-level data. The data cutoff date was May 31, 2024. Patients with mCRPC with evidence of harboring BRCA1/2 alterations and alive after August 15, 2020 (ie, 3 months after the approval of the first PARP inhibitor, rucaparib, in mCRPC) were included. Statistical analysis was performed from September 2024 to May 2025.</p><p><strong>Exposures: </strong>Age, race and ethnicity, insurance status, and practice type at the time of mCRPC diagnosis.</p><p><strong>Main outcomes and measures: </strong>The receipt of PARP inhibitors. Multivariable logistic regression was conducted to assess the association between the exposures and the main outcome.</p><p><strong>Results: </strong>Of 24 105 patients with metastatic prostate cancer, 443 male patients (median [IQR] age, 72 [65-79] years) had mCRPC with BRCA1/2 alterations and were eligible and included in our analysis. Of these patients, 227 (51.2%) received a PARP inhibitor, whereas 216 (48.8%) did not. Compared with patients covered by a commercial health plan, those covered by Medicare were significantly more likely to receive a PARP inhibitor (odds ratio, 1.91; 95% CI, 1.02-3.66; P = .047). The odds of receiving a PARP inhibitor were not significantly higher in patients treated in community practice compared with those treated in academic centers (odds ratio, 1.64; 95% CI, 1.00-2.70; P = .05).</p><p><strong>Conclusions and relevance: </strong>This retrospective cohort study of patients with mCRPC and evidence of BRCA1/2 alterations found that approximately half of patients did not receive PARP inhibitors despite evidence of survival improvement in this population. 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However, data are limited regarding the uptake of PARP inhibitors in these patients.</p><p><strong>Objective: </strong>To investigate the use of PARP inhibitors in patients with mCRPC harboring BRCA1/2 alterations.</p><p><strong>Design, setting, and participants: </strong>This retrospective cohort study used the deidentified Flatiron-Health electronic health record-derived database of US community and academic practices to extract patient-level data. The data cutoff date was May 31, 2024. Patients with mCRPC with evidence of harboring BRCA1/2 alterations and alive after August 15, 2020 (ie, 3 months after the approval of the first PARP inhibitor, rucaparib, in mCRPC) were included. Statistical analysis was performed from September 2024 to May 2025.</p><p><strong>Exposures: </strong>Age, race and ethnicity, insurance status, and practice type at the time of mCRPC diagnosis.</p><p><strong>Main outcomes and measures: </strong>The receipt of PARP inhibitors. 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引用次数: 0
摘要
重要性:具有BRCA1/2改变的转移性阉割抵抗性前列腺癌(mCRPC)患者有资格接受聚二磷酸腺苷核糖聚合酶(PARP)抑制剂作为单一药物或与雄激素受体途径抑制剂联合使用,因为这些药物在具有里程碑意义的临床试验中显示出生存改善。然而,这些患者对PARP抑制剂的摄取数据有限。目的:探讨PARP抑制剂在携带BRCA1/2改变的mCRPC患者中的应用。设计、环境和参与者:本回顾性队列研究使用美国社区和学术实践的未识别的Flatiron-Health电子健康记录衍生数据库来提取患者水平的数据。数据截止日期为2024年5月31日。有证据表明携带BRCA1/2改变且在2020年8月15日(即首个PARP抑制剂rucaparib在mCRPC中获批3个月后)存活的mCRPC患者被纳入研究。统计分析时间为2024年9月至2025年5月。暴露:年龄,种族和民族,保险状况,以及mCRPC诊断时的执业类型。主要结局和措施:接受PARP抑制剂治疗。采用多变量逻辑回归来评估暴露与主要结果之间的关系。结果:在24 105例转移性前列腺癌患者中,443例男性患者(中位[IQR]年龄,72[65-79]岁)的mCRPC伴有BRCA1/2改变,符合条件并纳入我们的分析。在这些患者中,227例(51.2%)接受了PARP抑制剂治疗,而216例(48.8%)未接受治疗。与商业健康计划覆盖的患者相比,医疗保险覆盖的患者更有可能接受PARP抑制剂(优势比,1.91;95% CI, 1.02-3.66; P = 0.047)。与在学术中心治疗的患者相比,在社区诊所治疗的患者接受PARP抑制剂的几率并没有显著增加(优势比1.64;95% CI, 1.00-2.70; P = 0.05)。结论和相关性:这项针对mCRPC患者和BRCA1/2改变证据的回顾性队列研究发现,尽管有证据表明该人群的生存改善,但约有一半的患者未接受PARP抑制剂治疗。这些发现强调了提高对mCRPC患者生存数据和获得延长生命治疗的认识的必要性。
Receipt of PARP Inhibitors in Patients With Metastatic Prostate Cancer Harboring BRCA1/2 Alterations.
Importance: Patients with metastatic castration-resistant prostate cancer (mCRPC) harboring BRCA1/2 alterations are eligible to receive poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitors as single agents or in combination with an androgen receptor pathway inhibitor after these agents showed survival improvement in their landmark clinical trials. However, data are limited regarding the uptake of PARP inhibitors in these patients.
Objective: To investigate the use of PARP inhibitors in patients with mCRPC harboring BRCA1/2 alterations.
Design, setting, and participants: This retrospective cohort study used the deidentified Flatiron-Health electronic health record-derived database of US community and academic practices to extract patient-level data. The data cutoff date was May 31, 2024. Patients with mCRPC with evidence of harboring BRCA1/2 alterations and alive after August 15, 2020 (ie, 3 months after the approval of the first PARP inhibitor, rucaparib, in mCRPC) were included. Statistical analysis was performed from September 2024 to May 2025.
Exposures: Age, race and ethnicity, insurance status, and practice type at the time of mCRPC diagnosis.
Main outcomes and measures: The receipt of PARP inhibitors. Multivariable logistic regression was conducted to assess the association between the exposures and the main outcome.
Results: Of 24 105 patients with metastatic prostate cancer, 443 male patients (median [IQR] age, 72 [65-79] years) had mCRPC with BRCA1/2 alterations and were eligible and included in our analysis. Of these patients, 227 (51.2%) received a PARP inhibitor, whereas 216 (48.8%) did not. Compared with patients covered by a commercial health plan, those covered by Medicare were significantly more likely to receive a PARP inhibitor (odds ratio, 1.91; 95% CI, 1.02-3.66; P = .047). The odds of receiving a PARP inhibitor were not significantly higher in patients treated in community practice compared with those treated in academic centers (odds ratio, 1.64; 95% CI, 1.00-2.70; P = .05).
Conclusions and relevance: This retrospective cohort study of patients with mCRPC and evidence of BRCA1/2 alterations found that approximately half of patients did not receive PARP inhibitors despite evidence of survival improvement in this population. These findings highlight the need to increase awareness of the survival data and access to life-prolonging therapies in patients with mCRPC.
期刊介绍:
JAMA Network Open, a member of the esteemed JAMA Network, stands as an international, peer-reviewed, open-access general medical journal.The publication is dedicated to disseminating research across various health disciplines and countries, encompassing clinical care, innovation in health care, health policy, and global health.
JAMA Network Open caters to clinicians, investigators, and policymakers, providing a platform for valuable insights and advancements in the medical field. As part of the JAMA Network, a consortium of peer-reviewed general medical and specialty publications, JAMA Network Open contributes to the collective knowledge and understanding within the medical community.