Department of Urology, Semmelweis University, Budapest, Hungary; Centre for Translational Medicine, Semmelweis University, Budapest, Hungary.
Centre for Translational Medicine, Semmelweis University, Budapest, Hungary; Institute for Translational Medicine, Medical School, University of Pécs, Pécs, Hungary.
Eur Urol Oncol. 2024 Jun;7(3):365-375. doi: 10.1016/j.euo.2023.09.001. Epub 2023 Sep 16.
Testing for mutations in Breast Cancer Gene 1/2 (BRCA) has emerged as a novel decision-making tool for clinicians. Patients with metastatic castration-resistant prostate cancer (mCRPC) harboring pathogenic BRCA mutations can benefit from poly (ADP-ribose) polymerase inhibitor (PARPi) and platinum treatments, whereas the impact of the mutation on sensitivity to cabazitaxel and prostate-specific membrane antigen (PSMA)-ligand therapy is currently unknown.
To assess the efficacy of PARPi, platinum, cabazitaxel, and PSMA-ligand therapies in BRCA-positive mCRPC.
Databases were queried in February 2022. We performed data synthesis by using both proportional and individual patient data. For prostate-specific antigen (PSA) response rate (≥50% decrease from baseline [PSA50]) evaluation, we pooled event rates with 95% confidence intervals (CIs). Progression-free (PFS) and overall (OS) survival analyses with individual patient data were performed with the mixed-effect Cox proportional hazard model and single-arm random-effect analysis, providing pooled medians.
We included 23 eligible studies with 901 BRCA-positive mCRPC patients. PSA50 response rates for PARPi and platinum were 69% (CI: 53-82%), and 74% (CI: 49-90%), respectively. Analyses of OS data showed no difference between PARPi and platinum treatments (hazard ratio: 0.86; CI: 0.49-1.52; p = 0.6). The single-arm OS and PFS analyses revealed similarities among different PARPis; pooled PFS and OS medians were 9.7 mo (CI: 8.1-12.5) and 17.4 mo (CI: 12.7-20.1), respectively.
Our data revealed that different PARPis were similarly effective in terms of PFS and OS. Moreover, we found that PARPi and platinum therapy were comparable in terms of PSA50 response rate and OS, highlighting that platinum is a valid treatment option for BRCA-positive mCRPC patients. However, prospective interventional studies comparing these agents are essential to provide a higher level of evidence.
In this report, we found that different poly (ADP-ribose) polymerase inhibitors had similar efficacy, and platinum was a valid treatment option in BRCA-positive metastatic castration-resistant prostate cancer patients.
乳腺癌基因 1/2（BRCA）突变检测已成为临床医生的一种新的决策工具。携带致病性 BRCA 突变的转移性去势抵抗性前列腺癌（mCRPC）患者可以受益于聚（ADP-核糖）聚合酶抑制剂（PARPi）和铂类治疗，而突变对卡巴他赛和前列腺特异性膜抗原（PSMA）配体治疗的敏感性的影响目前尚不清楚。
评估 PARPi、铂类、卡巴他赛和 PSMA 配体疗法在 BRCA 阳性 mCRPC 中的疗效。
2022 年 2 月检索数据库。我们通过比例和个体患者数据进行数据综合。对于前列腺特异性抗原（PSA）反应率（自基线下降≥50%[PSA50]）评估，我们用 95%置信区间（CI）汇总事件率。使用混合效应 Cox 比例风险模型和单臂随机效应分析对个体患者数据进行无进展生存期（PFS）和总生存期（OS）生存分析，提供汇总中位数。
我们纳入了 23 项有 901 例 BRCA 阳性 mCRPC 患者的合格研究。PARPi 和铂类的 PSA50 反应率分别为 69%（CI：53-82%）和 74%（CI：49-90%）。OS 数据分析显示，PARPi 和铂类治疗之间无差异（风险比：0.86；CI：0.49-1.52；p=0.6）。单臂 OS 和 PFS 分析表明，不同 PARPis 之间具有相似性；汇总的 PFS 和 OS 中位数分别为 9.7 个月（CI：8.1-12.5）和 17.4 个月（CI：12.7-20.1）。
我们的数据显示，不同的 PARPis 在 PFS 和 OS 方面同样有效。此外，我们发现 PARPi 和铂类治疗在 PSA50 反应率和 OS 方面相当，这突出表明铂类是 BRCA 阳性 mCRPC 患者的有效治疗选择。然而，比较这些药物的前瞻性干预研究至关重要，以提供更高水平的证据。
在本报告中，我们发现不同的聚（ADP-核糖）聚合酶抑制剂具有相似的疗效，铂类在 BRCA 阳性转移性去势抵抗性前列腺癌患者中是一种有效的治疗选择。
