Effectiveness of PARP Inhibitor Maintenance Therapy in Ovarian Cancer by BRCA1/2 and a Scar-Based HRD Signature in Real-World Practice.

IF 10 1区医学 Q1 ONCOLOGY

Clinical Cancer Research Pub Date : 2024-10-15 DOI:10.1158/1078-0432.CCR-24-1225

Debra L Richardson, Julia C F Quintanilha, Natalie Danziger, Gerald Li, Ethan Sokol, Alexa B Schrock, Ericka Ebot, Neeru Bhardwaj, Tanesha Norris, Anosheh Afghahi, Anthony Frachioni, Christina Washington, Lauren Dockery, Julia Elvin, Ryon P Graf, Kathleen N Moore

{"title":"Effectiveness of PARP Inhibitor Maintenance Therapy in Ovarian Cancer by BRCA1/2 and a Scar-Based HRD Signature in Real-World Practice.","authors":"Debra L Richardson, Julia C F Quintanilha, Natalie Danziger, Gerald Li, Ethan Sokol, Alexa B Schrock, Ericka Ebot, Neeru Bhardwaj, Tanesha Norris, Anosheh Afghahi, Anthony Frachioni, Christina Washington, Lauren Dockery, Julia Elvin, Ryon P Graf, Kathleen N Moore","doi":"10.1158/1078-0432.CCR-24-1225","DOIUrl":null,"url":null,"abstract":"Purpose: The purpose of the study was to compare the effectiveness of PARP inhibitor maintenance therapy (mPARPi) in real-world practice by biomarker status [BRCA1/2 alterations (BRCAalt) and a homologous recombination deficiency signature (HRDsig)] in advanced ovarian cancer.Experimental design: Patients with ovarian cancer receiving first-line platinum-based chemotherapy and either mPARPi or no maintenance were included. Patient data were obtained by a US-based de-identified ovarian cancer Clinico-Genomic Database, from ∼280 US cancer clinics (01/2015-03/2023). Real-world progression-free survival (rwPFS) and overall survival (rwOS) were compared by biomarker status using Cox models, weighted by propensity scores.Results: Of 673 patients, 160 received mPARPi [31.2% BRCAalt and 51.9% HRDsig(+)] and 513 no maintenance [15.6% BRCAalt and 34.1% HRDsig(+)]. BRCAalt patients receiving mPARPi versus no maintenance had favorable rwPFS [HR, 0.48; 95% confidence interval (CI), 0.26-0.87; P = 0.0154], as did BRCA wild-type (WT; HR, 0.76; 95% CI, 0.57-1.01; P = 0.0595). Favorable rwOS was not observed with mPARPi for BRCAalt or BRCA-WT. HRDsig(+) patients receiving mPARPi versus no maintenance had favorable rwPFS (HR, 0.36; 95% CI, 0.24-0.55; P < 0.001) and numerically favorable rwOS (HR, 0.46; 95% CI, 0.21-1.02; P = 0.0561). No differences were observed for HRDsig(-). mPARPi treatment interaction was observed for HRDsig(+) versus HRDsig(-) (rwPFS P < 0.001/rwOS P = 0.016) but not for BRCAalt versus BRCA-WT. Patients with BRCA-WT/HRDsig(+) receiving mPARPi had favorable rwPFS (HR, 0.40; 95% CI, 0.22-0.72; P = 0.003), whereas no difference was observed for BRCA-WT/HRDsig(-).Conclusions: HRDsig predicted benefit of mPARPi better than BRCAalt. Patients with HRDsig(+) status experienced favorable outcomes, even if they had BRCA-WT status. In contrast, patients with HRDsig(-) status did not show significant benefit from mPARPi treatment. HRDsig might predict benefit from mPARPi regardless of BRCAalt status.","PeriodicalId":10279,"journal":{"name":"Clinical Cancer Research","volume":" ","pages":"4644-4653"},"PeriodicalIF":10.0000,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11474169/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Clinical Cancer Research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1158/1078-0432.CCR-24-1225","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ONCOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Purpose: The purpose of the study was to compare the effectiveness of PARP inhibitor maintenance therapy (mPARPi) in real-world practice by biomarker status [BRCA1/2 alterations (BRCAalt) and a homologous recombination deficiency signature (HRDsig)] in advanced ovarian cancer.

Experimental design: Patients with ovarian cancer receiving first-line platinum-based chemotherapy and either mPARPi or no maintenance were included. Patient data were obtained by a US-based de-identified ovarian cancer Clinico-Genomic Database, from ∼280 US cancer clinics (01/2015-03/2023). Real-world progression-free survival (rwPFS) and overall survival (rwOS) were compared by biomarker status using Cox models, weighted by propensity scores.

Results: Of 673 patients, 160 received mPARPi [31.2% BRCAalt and 51.9% HRDsig(+)] and 513 no maintenance [15.6% BRCAalt and 34.1% HRDsig(+)]. BRCAalt patients receiving mPARPi versus no maintenance had favorable rwPFS [HR, 0.48; 95% confidence interval (CI), 0.26-0.87; P = 0.0154], as did BRCA wild-type (WT; HR, 0.76; 95% CI, 0.57-1.01; P = 0.0595). Favorable rwOS was not observed with mPARPi for BRCAalt or BRCA-WT. HRDsig(+) patients receiving mPARPi versus no maintenance had favorable rwPFS (HR, 0.36; 95% CI, 0.24-0.55; P < 0.001) and numerically favorable rwOS (HR, 0.46; 95% CI, 0.21-1.02; P = 0.0561). No differences were observed for HRDsig(-). mPARPi treatment interaction was observed for HRDsig(+) versus HRDsig(-) (rwPFS P < 0.001/rwOS P = 0.016) but not for BRCAalt versus BRCA-WT. Patients with BRCA-WT/HRDsig(+) receiving mPARPi had favorable rwPFS (HR, 0.40; 95% CI, 0.22-0.72; P = 0.003), whereas no difference was observed for BRCA-WT/HRDsig(-).

Conclusions: HRDsig predicted benefit of mPARPi better than BRCAalt. Patients with HRDsig(+) status experienced favorable outcomes, even if they had BRCA-WT status. In contrast, patients with HRDsig(-) status did not show significant benefit from mPARPi treatment. HRDsig might predict benefit from mPARPi regardless of BRCAalt status.

查看原文本刊更多论文

根据 BRCA1/2 和基于疤痕的 HRD 特征在现实世界中对卵巢癌进行 PARP 抑制剂维持治疗的有效性。

目的根据晚期卵巢癌（OC）患者的生物标志物状态（BRCA1/2改变[BRCAalt]和同源重组缺陷特征[HRDsig]），比较PARP抑制剂维持疗法（mPARPi）在实际应用中的有效性：方法：纳入接受一线铂类化疗和 mPARPi 或无维持治疗的卵巢癌患者。患者数据来自美国的去标识化卵巢癌临床基因组数据库，该数据库来自约 280 家美国癌症诊所（01/2015-03/2023）。使用Cox模型，按倾向得分加权，比较了生物标记物状态下的实际无进展生存期（rwPFS）和总生存期（rwOS）：673例患者中，160例接受了mPARPi治疗[31.2%为BRCAalt，51.9%为HRDsig(+)]，513例未接受维持治疗[15.6%为BRCAalt，34.1%为HRDsig(+)]。接受 mPARPi 治疗的 BRCAalt 患者与不接受治疗的患者相比，rwPFS 较好（HR 0.48，95%CI 0.26-0.87，p=0.0154），BRCA 野生型（wt）患者也是如此（HR 0.76，95%CI 0.57-1.01，p=0.0595）。对于 BRCAalt 或 BRCAwt，使用 mPARPi 未观察到有利的 rwOS。接受mPARPi治疗的HRDsig（+）患者与不接受mPARPi治疗的患者相比，rwPFS较好（HR为0.36，95%CI为0.24-0.55，P=0.0595）：HRDsig比BRCAalt更能预测mPARPi的获益情况。即使在 BRCAwt 患者中，HRDsig(+) 患者也能获得良好的预后，而 HRDsig(-) 患者则没有显示出 mPARPi 的获益丰富性。无论 BRCAalt 状态如何，HRDsig 都能预测 mPARPi 的获益情况。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Clinical Cancer Research 医学-肿瘤学

CiteScore

20.10

自引率

1.70%

发文量

1207

审稿时长

2.1 months

期刊介绍： Clinical Cancer Research is a journal focusing on groundbreaking research in cancer, specifically in the areas where the laboratory and the clinic intersect. Our primary interest lies in clinical trials that investigate novel treatments, accompanied by research on pharmacology, molecular alterations, and biomarkers that can predict response or resistance to these treatments. Furthermore, we prioritize laboratory and animal studies that explore new drugs and targeted agents with the potential to advance to clinical trials. We also encourage research on targetable mechanisms of cancer development, progression, and metastasis.