ImportanceOlaparib 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.ObjectiveTo determine the activity of olaparib monotherapy among patients with high-risk biochemically recurrent (BCR) prostate cancer after radical prostatectomy.Design, Setting, and ParticipantsThis 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.InterventionTreatment 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 MeasureThe 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.ResultsOf 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 RelevanceIn 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 RegistrationClinicalTrials.gov Identifier: NCT03047135

中文翻译：

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奥拉帕尼不剥夺雄激素治疗前列腺切除术后高危生化复发性前列腺癌


重要性奥拉帕尼是一种聚（腺苷二磷酸-核糖）聚合酶抑制剂，与激素治疗联合治疗对携带同源重组修复 （HRR） 改变的转移性前列腺癌患者有益。其在没有雄激素剥夺治疗的情况下的疗效尚未得到检验。目的确定奥拉帕尼单药治疗根治性前列腺切除术后高危生化复发 （BCR） 前列腺癌患者的疗效。设计、设置和参与者这项 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 个地点招募了未经选择的遗传患者。符合条件的患者在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，绝对 PSA 值为 1.0 ng/mL 或更高，睾酮水平为 150 ng/dL 或更高。干预治疗为奥拉帕尼 300 毫克，每天两次口服，直到基线 PSA 翻倍、临床或影像学进展或不可接受的毒性作用。主要结局和测量主要终点是确认 PSA 较基线 （PSA50） 下降 50% 或更高。关键的次要终点是 HRR 改变状态以及安全性和耐受性的结局。结果在入组的 51 名男性患者 （平均 [SD] 年龄，63.8 [6.8] 岁） 中，13 名参与者 （26%） 有 PSA50 反应，均属于 HRR 阳性组 （27 名参与者中的 13 名 [48%]）。所有 11 名 BRCA2 改变的参与者都经历了 PSA50 反应。常见的不良事件是 32 名参与者 （63%） 的疲劳、28 名 （55%） 的恶心和 22 名 （43%） 的白细胞减少，并且与奥拉帕尼的已知不良反应一致。结论和相关性在这项非随机对照试验中，奥拉帕尼单药治疗导致 BRCA2 改变患者的 PSA50 反应率高且持久。奥拉帕尼值得进一步研究作为一些 BCR 前列腺癌患者的治疗策略，但在没有 HRR 改变的患者中没有足够的活性，因此不应考虑用于这些患者。试验注册临床试验。gov 标识符： NCT03047135