Mirat Shah, Ting-Yu Chen, Gwynn Ison, Mallorie H Fiero, Hui Zhang, Xin Gao, Marc Neilson, Kirsten B Goldberg, Abhilasha Nair, Tiffany K Ricks, William F Pierce, Nicole Gormley, Marc R Theoret, Shenghui Tang, Richard Pazdur, Paul G Kluetz, Laleh Amiri-Kordestani
{"title":"Overall Survival and the Evolving Benefit-Risk Assessment for Poly (ADP-ribose) Polymerase Inhibitors in Advanced Ovarian Cancer.","authors":"Mirat Shah, Ting-Yu Chen, Gwynn Ison, Mallorie H Fiero, Hui Zhang, Xin Gao, Marc Neilson, Kirsten B Goldberg, Abhilasha Nair, Tiffany K Ricks, William F Pierce, Nicole Gormley, Marc R Theoret, Shenghui Tang, Richard Pazdur, Paul G Kluetz, Laleh Amiri-Kordestani","doi":"10.1200/JCO-24-02834","DOIUrl":null,"url":null,"abstract":"<p><p>From 2014 through 2019, the US Food and Drug Administration (FDA) granted approval to six indications for poly (ADP-ribose) polymerase (PARP) inhibitors in advanced epithelial ovarian cancer (EOC). From 2022 through 2023, these six indications were withdrawn or narrowed after observation of a potential detrimental effect on overall survival (OS) in four randomized controlled trials. The indications for niraparib, olaparib, and rucaparib for the treatment of <i>BRCA</i>-mutated or homologous recombination deficiency-positive advanced EOC were withdrawn. The indications for niraparib, olaparib, and rucaparib for the maintenance treatment of recurrent EOC were narrowed to only patients with <i>BRCA</i> mutations. Recognizing the clinical implications of these regulatory actions, herein we describe the FDA's decision-making process and the rationale behind the removal or narrowing of these indications for PARP inhibitors in advanced EOC. Furthermore, this article provides insight into the FDA's interpretation of potential OS detriments and subgroup analyses to shape regulatory decisions.</p>","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"2218-2227"},"PeriodicalIF":42.1000,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Clinical Oncology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1200/JCO-24-02834","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/5/19 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"ONCOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
From 2014 through 2019, the US Food and Drug Administration (FDA) granted approval to six indications for poly (ADP-ribose) polymerase (PARP) inhibitors in advanced epithelial ovarian cancer (EOC). From 2022 through 2023, these six indications were withdrawn or narrowed after observation of a potential detrimental effect on overall survival (OS) in four randomized controlled trials. The indications for niraparib, olaparib, and rucaparib for the treatment of BRCA-mutated or homologous recombination deficiency-positive advanced EOC were withdrawn. The indications for niraparib, olaparib, and rucaparib for the maintenance treatment of recurrent EOC were narrowed to only patients with BRCA mutations. Recognizing the clinical implications of these regulatory actions, herein we describe the FDA's decision-making process and the rationale behind the removal or narrowing of these indications for PARP inhibitors in advanced EOC. Furthermore, this article provides insight into the FDA's interpretation of potential OS detriments and subgroup analyses to shape regulatory decisions.
期刊介绍:
The Journal of Clinical Oncology serves its readers as the single most credible, authoritative resource for disseminating significant clinical oncology research. In print and in electronic format, JCO strives to publish the highest quality articles dedicated to clinical research. Original Reports remain the focus of JCO, but this scientific communication is enhanced by appropriately selected Editorials, Commentaries, Reviews, and other work that relate to the care of patients with cancer.