在 PROpel (NCT03732820) 中，与安慰剂阿比特龙相比，奥拉帕尼阿比特龙在一线 (1L) 转移性去势抵抗性前列腺癌 (mCRPC) 患者中产生了统计学上显着的影像学无进展生存期 (rPFS) 益处，并在数值上延长了总生存期 (OS) 。在此，我们报告对基线时无症状/轻度症状或有症状疾病的患者进行事后探索性亚组分析。患者按 1:1 随机分配至奥拉帕尼（300 mg b.i.d.）或安慰剂加阿比特龙（1000 mg o.d.）泼尼松/泼尼松龙（5 mg）出价。）。对于这项事后探索性分析，简短疼痛清单 (BPI-SF) 第 3 项评分 <4 且未使用阿片类药物的患者被分类为无症状/轻度症状； BPI-SF 第 3 项评分≥4 和/或使用阿片类药物的患者被归类为有症状的患者。亚组分析包括研究者评估的 rPFS、OS、客观缓解率、第二次进展或死亡时间、健康相关生活质量和安全性。奥拉帕尼组无症状/轻度症状患者 (n = 560) 的中位 rPFS 为 27.6 个月阿比特龙与安慰剂阿比特龙 19.1 个月相比（风险比 [HR]，0.59；95% 置信区间 [CI]，0.46-0.76）。对于有症状的患者 (n = 183)，等效值为 14.1 个月与 13.8 个月（HR，0.78；95% CI，0.54-1.13）。在最终计划的 OS 分析中，奥拉帕尼阿比特龙组未达到无症状/轻度症状患者的中位 OS，而安慰剂阿比特龙组为 39.5 个月（HR，0.77；95% CI，0.59-1.00）。对于有症状的患者，等效值为 22.9 个月与 22.8 个月（HR，0.82；95% CI，0.58-1.16）。其他结果显示亚组之间没有显着差异。奥拉帕尼阿比特龙为无症状/轻度症状或有症状疾病的 1L mCRPC 患者提供了疗效益处。无症状/轻度症状患者获益更大。PROpel 是一项 3 期临床试验，研究与安慰剂加阿比特龙相比，奥拉帕尼与阿比特龙联合治疗是否能延缓患者癌症的进展。有或没有与转移性去势抵抗性前列腺癌相关的疼痛症状的患者都有资格参加该试验。结果显示，奥拉帕尼联合阿比特龙降低了疾病进展和死亡的风险，在没有或有轻微疼痛症状的患者中观察到的益处比有疼痛症状的患者更大。版权所有 © 2024 作者。由 Elsevier B.V. 出版。保留所有权利。

In PROpel (NCT03732820), olaparib + abiraterone resulted in a statistically significant radiographic progression-free survival (rPFS) benefit and numerically prolonged overall survival (OS) versus placebo + abiraterone in first-line (1L) metastatic castration-resistant prostate cancer (mCRPC) patients. Here, we report post hoc exploratory subgroup analyses in patients with asymptomatic/mildly symptomatic or symptomatic disease at baseline.Patients were randomised 1:1 to olaparib (300 mg b.i.d.) or placebo with abiraterone (1000 mg o.d.) + prednisone/prednisolone (5 mg b.i.d.). For this post hoc exploratory analysis, patients with a Brief Pain Inventory-Short Form (BPI-SF) item 3 score of <4 and no opiate use were classified as asymptomatic/mildly symptomatic; those with a BPI-SF item 3 score of ≥4 and/or opiate use were classified as symptomatic. Subgroup analyses included investigator-assessed rPFS, OS, objective response rate, time to second progression or death, health-related quality of life, and safety.The median rPFS in asymptomatic/mildly symptomatic patients (n = 560) was 27.6 mo for olaparib + abiraterone versus 19.1 mo for placebo + abiraterone (hazard ratio [HR], 0.59; 95% confidence interval [CI], 0.46-0.76). For symptomatic patients (n = 183), equivalent values were 14.1 versus 13.8 mo (HR, 0.78; 95% CI, 0.54-1.13). At the final planned OS analysis, the median OS in asymptomatic/mildly symptomatic patients was not reached for olaparib + abiraterone versus 39.5 mo for placebo + abiraterone (HR, 0.77; 95% CI, 0.59-1.00). For symptomatic patients, equivalent values were 22.9 versus 22.8 mo (HR, 0.82; 95% CI, 0.58-1.16). Other outcomes showed no meaningful differences between the subgroups.Olaparib + abiraterone provided efficacy benefits in 1L mCRPC patients with either asymptomatic/mildly symptomatic or symptomatic disease. A larger benefit occurred in asymptomatic/mildly symptomatic patients.PROpel, a phase 3 clinical trial, looked at whether combining olaparib with abiraterone delays the progression of patients' cancer compared with placebo plus abiraterone. Patients with or without pain symptoms associated with metastatic castration-resistant prostate cancer were eligible for enrolment into the trial. Results showed that olaparib plus abiraterone reduced the risk of disease progression and death, with a larger benefit observed in patients without or with mild pain symptoms than in those with pain symptoms.Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.