Olaparib Without Androgen Deprivation for High-Risk Biochemically Recurrent Prostate Cancer Following Prostatectomy: A Nonrandomized Controlled Trial.

IF 28.4 1区医学 Q1 Biochemistry, Genetics and Molecular Biology

Jama Oncology Pub Date : 2024-10-01 DOI:10.1001/jamaoncol.2024.3074

Catherine H Marshall, Benjamin A Teply, Jiayun Lu, Lia Oliveira, Hao Wang, Shifeng S Mao, W Kevin Kelly, Channing J Paller, Mark C Markowski, Samuel R Denmeade, Serina King, Rana Sullivan, Elai Davicioni, James A Proudfoot, Mario A Eisenberger, Michael A Carducci, Tamara L Lotan, Emmanuel S Antonarakis

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引用次数: 0

Abstract

Importance: Olaparib is a poly(adenosine diphosphate-ribose) polymerase inhibitor that provides benefit in combination with hormonal therapies in patients with metastatic prostate cancer who harbor homologous recombination repair (HRR) alterations. Its efficacy in the absence of androgen deprivation therapy has not been tested.

Objective: To determine the activity of olaparib monotherapy among patients with high-risk biochemically recurrent (BCR) prostate cancer after radical prostatectomy.

Design, setting, and participants: This phase 2, single-arm nonrandomized controlled trial enrolled genetically unselected patients across 4 sites in the US from May 2017 to November 2022. Eligible patients had BCR disease following radical prostatectomy, a prostate-specific antigen (PSA) doubling time of 6 months or shorter, an absolute PSA value of 1.0 ng/mL or higher, and a testosterone level of 150 ng/dL or higher.

Intervention: Treatment was with olaparib, 300 mg, by mouth twice daily until doubling of the baseline PSA, clinical or radiographic progression, or unacceptable toxic effects.

Main outcome and measure: The primary end point was a confirmed 50% or higher decline in PSA from baseline (PSA50). Key secondary end points were outcomes by HRR alteration status, as well as safety and tolerability.

Results: Of the 51 male patients enrolled (mean [SD] age, 63.8 [6.8] years), 13 participants (26%) had a PSA50 response, all within the HRR-positive group (13 of 27 participants [48%]). All 11 participants with BRCA2 alterations experienced a PSA50 response. Common adverse events were fatigue in 32 participants (63%), nausea in 28 (55%), and leukopenia in 22 (43%), and were consistent with known adverse effects of olaparib.

Conclusions and relevance: In this nonrandomized controlled trial, olaparib monotherapy led to high and durable PSA50 response rates in patients with BRCA2 alterations. Olaparib warrants further study as a treatment strategy for some patients with BCR prostate cancer but does not have sufficient activity in those without HRR alterations and should not be considered for those patients.

Trial registration: ClinicalTrials.gov Identifier: NCT03047135.

查看原文本刊更多论文

前列腺切除术后高风险生化复发前列腺癌的奥拉帕利（Olaparib）和雄激素剥夺治疗：一项非随机对照试验。

重要意义奥拉帕利（Olaparib）是一种多聚腺苷二磷酸核糖聚合酶抑制剂，与激素疗法联合使用可为携带同源重组修复（HRR）改变的转移性前列腺癌患者带来益处。它在没有雄激素剥夺疗法的情况下的疗效尚未得到测试：目的：确定奥拉帕利单药治疗根治性前列腺切除术后高危生化复发（BCR）前列腺癌患者的活性：这项2期单臂非随机对照试验于2017年5月至2022年11月在美国的4个地点招募了未经基因筛选的患者。符合条件的患者在接受根治性前列腺切除术后患有BCR疾病，前列腺特异性抗原（PSA）倍增时间为6个月或更短，PSA绝对值为1.0纳克/毫升或更高，睾酮水平为150纳克/分升或更高：主要结果和测量指标：主要终点是PSA从基线下降50%或以上（PSA50）。主要次要终点是根据 HRR 改变状况得出的结果，以及安全性和耐受性：入组的 51 名男性患者（平均 [SD] 年龄为 63.8 [6.8] 岁）中，有 13 名患者（26%）的 PSA50 出现了反应，他们都属于 HRR 阳性组（27 人中有 13 人 [48%]）。所有 11 名 BRCA2 基因改变的参与者都出现了 PSA50 反应。常见的不良反应有32人（63%）出现疲劳，28人（55%）出现恶心，22人（43%）出现白细胞减少，这些不良反应与奥拉帕利的已知不良反应一致：在这项非随机对照试验中，奥拉帕利单药治疗对 BRCA2 基因改变患者的 PSA50 反应率高且持久。奥拉帕利值得作为某些BCR前列腺癌患者的治疗策略进行进一步研究，但对无HRR改变的患者没有足够的活性，因此这些患者不应考虑奥拉帕利：试验注册：ClinicalTrials.gov Identifier：NCT03047135。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Jama Oncology Medicine-Oncology

CiteScore

37.50

自引率

1.80%

发文量

423

期刊介绍： At JAMA Oncology, our primary goal is to contribute to the advancement of oncology research and enhance patient care. As a leading journal in the field, we strive to publish influential original research, opinions, and reviews that push the boundaries of oncology science. Our mission is to serve as the definitive resource for scientists, clinicians, and trainees in oncology globally. Through our innovative and timely scientific and educational content, we aim to provide a comprehensive understanding of cancer pathogenesis and the latest treatment advancements to our readers. We are dedicated to effectively disseminating the findings of significant clinical research, major scientific breakthroughs, actionable discoveries, and state-of-the-art treatment pathways to the oncology community. Our ultimate objective is to facilitate the translation of new knowledge into tangible clinical benefits for individuals living with and surviving cancer.