奥拉帕尼是一种聚（腺苷二磷酸核糖）聚合酶抑制剂，与激素疗法联合使用，可为具有同源重组修复（HRR）改变的转移性前列腺癌患者带来益处。尚未测试其在没有雄激素剥夺治疗的情况下的疗效。旨在确定奥拉帕尼单药治疗在根治性前列腺切除术后高危生化复发 (BCR) 前列腺癌患者中的活性。这项 2 期、单臂非随机对照试验以基因方式入组2017 年 5 月至 2022 年 11 月期间，美国 4 个地点的未选择患者。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 或较高，且睾酮水平为 150 ng/dL 或更高。治疗采用奥拉帕尼 300 mg，每天口服两次，直至基线 PSA 加倍、临床或放射学进展或不可接受的毒性作用。主要终点是已确认的PSA 较基线 (PSA50) 下降 50% 或更高。关键的次要终点是 HRR 改变状态的结果，以及安全性和耐受性。 在入组的 51 名男性患者中（平均 [SD] 年龄，63.8 [6.8] 岁），13 名参与者 (26%) 出现 PSA50 反应，全部HRR 阳性组（27 名参与者中的 13 名 [48%]）。所有 11 名患有 BRCA2 变异的参与者都经历了 PSA50 反应。常见的不良事件包括 32 名参与者 (63%) 的疲劳、28 名参与者 (55%) 的恶心和 22 名参与者 (43%) 的白细胞减少，这些事件与奥拉帕尼的已知不良反应一致。 在这项非随机对照试验中，奥拉帕尼单一疗法导致BRCA2 变异患者的 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，但对于那些没有 HRR 改变的患者没有足够的活性，因此不应考虑用于这些患者。ClinicalTrials.gov 标识符：NCT03047135。

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.To determine the activity of olaparib monotherapy among patients with high-risk biochemically recurrent (BCR) prostate cancer after radical prostatectomy.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.Treatment was with olaparib, 300 mg, by mouth twice daily until doubling of the baseline PSA, clinical or radiographic progression, or unacceptable toxic effects.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.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.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.ClinicalTrials.gov Identifier: NCT03047135.