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":"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。","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":"<p><strong>Purpose: </strong>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.</p><p><strong>Experimental design: </strong>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.</p><p><strong>Results: </strong>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(-).</p><p><strong>Conclusions: </strong>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.</p>","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":"{\"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\":\"<p><strong>Purpose: </strong>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.</p><p><strong>Experimental design: </strong>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.</p><p><strong>Results: </strong>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(-).</p><p><strong>Conclusions: </strong>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.</p>\",\"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}","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}
Effectiveness of PARP Inhibitor Maintenance Therapy in Ovarian Cancer by BRCA1/2 and a Scar-Based HRD Signature in Real-World Practice.
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.
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.
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