Clinical Outcome of Prostate Cancer Patients with Germline DNA Repair Mutations: Retrospective Analysis from an International Study.
Clinical Outcome of Prostate Cancer Patients with Germline DNA Repair Mutations: Retrospective Analysis from an International Study.
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DOI：
10.1016/j.eururo.2018.01.010
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发表时间：
2018-05
期刊：
影响因子：
23.4
通讯作者：
de Bono JS
中科院分区：
文献类型：
--
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
在10%的转移性前列腺癌(MPC)中发现生殖系DNA损伤修复基因突变(GDDRm)。它们与标准疗法相关的预后和预测性影响尚不清楚。确定gDDRm状态影响是否受益于MPC中已有的疗法。这是一项回溯性、国际性、观察性研究。回顾了390名已知GDDRm状态的MPC患者的医疗记录。来自Royal Marsden(英国)、Weill-Cornell(NY)和华盛顿大学(WA)的372名患者都曾被纳入患病率研究(Pritchard，NEJM 2016)；其余18名患者是来自澳大利亚kConFab财团的gBRCA1/200万携带者。收集有效率(RR)、无进展生存期(PFS)和总生存期(OS)数据。为了解释队列之间的潜在差异，使用了每个队列具有随机截获的混合效应模型(威布尔分布)。所有390名患者都知道gDDRm状态(60名gDDRm携带者[gDDRm+]，包括37名gBRCA2m，330例未发现gDDRm[gDDRm-])；74%和69%的患者分别接受了多西紫杉醇和阿比特龙/苯扎鲁胺的治疗，36%的患者接受了PARP抑制剂(PARPI)和/或铂类药物的治疗。去势抵抗组的中位OS相似(3.2vs3.0年，p=0.73)。多西紫杉醇对gDDRm+和gDDRm-的中位PFS分别为6.8mo和5.1mo，RRS相似(gDDRm+=61%；gDDRm-=54%)。一线阿比特龙/苯扎鲁胺的中位PFS和RR差异无统计学意义(gDDRm+=8.3mo，gDDRm-=8.3mo；gDDRm+=46%，gDDRm-=56%)。PARPI/白金和gDDRm+的相互作用测试得出OS调整后的危险比为0.59(95%可信区间为0.28-1.25；p=0.17)。结果受到分析的回溯性的限制。患有gDDRm的MPC患者似乎与总体人群一样从标准治疗中受益；前瞻性研究正在进行中，以调查PARPI/白金的影响。具有遗传DNA修复突变的患者与其他转移性前列腺癌患者一样，从标准治疗中受益。
Germline DNA damage repair gene mutation (gDDRm) is found in >10% of metastatic prostate cancer (mPC). Their prognostic and predictive impact relating to standard therapies is unclear. To determine whether gDDRm status impacts benefit from established therapies in mPC. This is a retrospective, international, observational study. Medical records were reviewed for 390 mPC patients with known gDDRm status. All 372 patients from Royal Marsden (UK), Weill-Cornell (NY), and University of Washington (WA) were previously included in a prevalence study (Pritchard, NEJM 2016); the remaining 18 were gBRCA1/2m carriers, from the kConFab consortium, Australia. Response rate (RR), progression-free survival (PFS), and overall survival (OS) data were collected. To account for potential differences between cohorts, a mixed-effect model (Weibull distribution) with random intercept per cohort was used. The gDDRm status was known for all 390 patients (60 carriers of gDDRm [gDDRm +], including 37 gBRCA2m, and 330 cases not found to carry gDDRm [gDDRm–]); 74% and 69% were treated with docetaxel and abiraterone/enzalutamide, respectively, and 36% received PARP inhibitors (PARPi) and/or platinum. Median OS from castration resistance was similar among groups (3.2vs 3.0 yr, p = 0.73). Median docetaxel PFS for gDDRm+ (6.8 mo) was not significantly different from that for gDDRm- (5.1 mo), and RRs were similar (gDDRm+ = 61%; gDDRm- = 54%). There were no significant differences in median PFS and RR on first-line abiraterone/enzalutamide (gDDRm+ = 8.3 mo, gDDRm- = 8.3 mo; gDDRm+ = 46%, gDDRm- = 56%). Interaction test for PARPi/platinum and gDDRm+ resulted in an OS adjusted hazard ratio of 0.59 (95% confidence interval 0.28–1.25; p = 0.17). Results are limited by the retrospective nature of the analysis. mPC patients with gDDRm appeared to benefit from standard therapies similarly to the overall population; prospective studies are ongoing to investigate the impact of PARPi/platinum. Patients with inherited DNA repair mutations benefit from standard therapies similarly to other metastatic prostate cancer patients.
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影响因子：
64.5
作者：
Cancer Genome Atlas Research Network
通讯作者：
Cancer Genome Atlas Research Network
影响因子：
4.6
作者：
Abida W;Armenia J;Gopalan A;Brennan R;Walsh M;Barron D;Danila D;Rathkopf D;Morris M;Slovin S;McLaughlin B;Curtis K;Hyman DM;Durack JC;Solomon SB;Arcila ME;Zehir A;Syed A;Gao J;Chakravarty D;Vargas HA;Robson ME;Joseph V;Offit K;Donoghue MTA;Abeshouse AA;Kundra R;Heins ZJ;Penson AV;Harris C;Taylor BS;Ladanyi M;Mandelker D;Zhang L;Reuter VE;Kantoff PW;Solit DB;Berger MF;Sawyers CL;Schultz N;Scher HI
通讯作者：
Scher HI
铂敏感转移性去势抵抗性前列腺癌中 BRCA2 的双等位基因失活。
影响因子：
23.4
作者：
Cheng HH;Pritchard CC;Boyd T;Nelson PS;Montgomery B
通讯作者：
Montgomery B
影响因子：
23.4
作者：
Castro, Elena;Goh, Chee;Eeles, Rosalind
通讯作者：
Eeles, Rosalind
影响因子：
4.5
作者：
Gallagher, David J.;Cronin, Angel M.;Robson, Mark E.
通讯作者：
Robson, Mark E.