Therapeutic sensitivity to standard treatments in BRCA positive metastatic castration-resistant prostate cancer patients-a systematic review and meta-analysis.
Therapeutic sensitivity to standard treatments in BRCA positive metastatic castration-resistant prostate cancer patients-a systematic review and meta-analysis.
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DOI：
10.1038/s41391-022-00626-2
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发表时间：
2023-12
影响因子：
4.8
通讯作者：
Szarvas, Tibor
中科院分区：
文献类型：
--
作者：
Fazekas, Tamas;Szeles, Adam D.;Teutsch, Brigitta;Csizmarik, Anita;Vekony, Balint;Varadi, Alex;Koi, Tamas;Lang, Zsolt;Acs, Nandor;Kopa, Zsolt;Hegyi, Peter;Hadaschik, Boris;Gruenwald, Viktor;Nyirady, Peter;Szarvas, Tibor
最近的肿瘤学指南建议BRCA 1/2检测广泛的前列腺癌（PCa）患者。此外，PARP抑制剂可用于既往接受阿比特龙、Enzalutamide或多西他赛治疗后突变阳性转移性去势抵抗性PCa（mCRPC）患者。然而，这些标准治疗中哪一种对BRCA 1/2阳性mCRPC患者最有效的问题仍有待回答。本荟萃分析的目的是评估阿比特龙、Enzalutamide和多西他赛在BRCA 1/2突变阳性mCRPC患者中PSA缓解（PSA 50）、无进展生存期（PFS）和总生存期（OS）方面的疗效。由于没有关于该主题的干预性试验，我们使用比例和个体患者数据对BRCA 1/2阳性mCRPC患者进行了数据合成。对于PSA 50评价，我们将事件发生率与95%置信区间（CI）合并，而对于至事件发生时间（PFS、OS）分析，我们使用个体患者数据与随机效应考克斯回归计算。我们的荟萃分析包括16项合格研究，348例BRCA 1/2阳性mCRPC患者。一线治疗中，阿比特龙、Enzalutamide和多西他赛的缓解率分别为52%（CI：25-79%）、64%（CI：43-80%）和55%（CI：36-73%）。个体患者数据分析显示，与阿比特龙治疗患者相比，enzalutamide治疗患者具有PFS（HR：0.47，CI：0.26-0.83，p = 0.010）获益，但无OS（HR：1.41，CI：0.82-2.42，p = 0.210）获益。我们的PSA 50分析显示，所有三种一线治疗对BRCA 1/2阳性mCRPC均有治疗作用;尽管根据PSA 50和PFS分析结果，BRCA阳性mCRPC患者可能对Enzalutamide治疗有更好的应答。然而，直接比较这些药物的分子标志物驱动的干预性研究对于提供更高水平的证据至关重要。
Recent oncology guidelines recommend BRCA1/2 testing for a wide range of prostate cancer (PCa) patients. In addition, PARP inhibitors are available for mutation-positive metastatic castration-resistant PCa (mCRPC) patients following prior treatment with abiraterone, enzalutamide or docetaxel. However, the question of which of these standard treatments is the most effective for BRCA1/2 positive mCRPC patients remains to be answered. The aim of this meta-analysis was to assess the efficacy of abiraterone, enzalutamide and docetaxel in BRCA1/2 mutation-positive mCRPC patients in terms of PSA-response (PSA50), progression-free survival (PFS) and overall survival (OS). As no interventional trials are available on this topic, we performed the data synthesis of BRCA1/2 positive mCRPC patients by using both proportional and individual patient data. For PSA50 evaluation, we pooled event rates with 95% confidence intervals (CI), while for time-to-event (PFS, OS) analyses we used individual patient data with random effect Cox regression calculations. Our meta-analysis included 16 eligible studies with 348 BRCA1/2 positive mCRPC patients. In the first treatment line, response rates for abiraterone, enzalutamide and docetaxel were 52% (CI: 25–79%), 64% (CI: 43–80%) and 55% (CI: 36–73%), respectively. Analyses of individual patient data revealed a PFS (HR: 0.47, CI: 0.26–0.83, p = 0.010) but no OS (HR: 1.41, CI: 0.82–2.42, p = 0.210) benefit for enzalutamide compared to abiraterone-treated patients. Our PSA50 analyses revealed that all the three first-line treatments have therapeutic effect in BRCA1/2 positive mCRPC; although, based on the results of PSA50 and PFS analyses, BRCA positive mCRPC patients might better respond to enzalutamide treatment. However, molecular marker-driven interventional studies directly comparing these agents are crucial for providing higher-level evidence.
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影响因子：
23.4
作者：
Mateo J;Cheng HH;Beltran H;Dolling D;Xu W;Pritchard CC;Mossop H;Rescigno P;Perez-Lopez R;Sailer V;Kolinsky M;Balasopoulou A;Bertan C;Nanus DM;Tagawa ST;Thorne H;Montgomery B;Carreira S;Sandhu S;Rubin MA;Nelson PS;de Bono JS
通讯作者：
de Bono JS
影响因子：
51.1
作者：
Khalaf, Daniel J.;Annala, Matti;Chi, Kim N.
通讯作者：
Chi, Kim N.
影响因子：
45.3
作者：
Ballman, Karla V.
通讯作者：
Ballman, Karla V.
DOI：
10.6004/jnccn.2020.7663
发表时间：
2021-08-01
影响因子：
13.4
作者：
Dong, Baijun;Fan, Liancheng;Xue, Wei
通讯作者：
Xue, Wei
影响因子：
4.5
作者：
Gallagher, David J.;Cronin, Angel M.;Robson, Mark E.
通讯作者：
Robson, Mark E.