a Department of Gynecologic Oncology , Fondazione IRCCS Istituto Nazionale dei Tumori , Milan , Italy.
Expert Opin Pharmacother. 2018 May;19(7):765-771. doi: 10.1080/14656566.2018.1464557. Epub 2018 Apr 19.
Approximately 50% of high-grade serous ovarian cancers present a deficiency in the pathways involved in homologous recombination (HR). PARP inhibitors prevent single-strand DNA damage repair and determine a progression of the defect towards double-strand breaks, which results in a process known as 'synthetic lethality'. Areas covered: In this review, the authors discuss the efficacy and toxicity of rucaparib either as a single agent or as a maintenance treatment for ovarian cancer. This includes the NGS Foundation Medicine evaluation of the role of this drug in the treatment algorithm of ovarian cancer. Moreover, perspectives on the future development of this drug are presented. Expert opinion: The FDA has approved this drug for the treatment of recurrent BRCA-mutated ovarian cancers, which were previously treated with at least two chemotherapies and has accepted the supplemental new drug application for maintenance use in patients who respond to platinum-based chemotherapy via the Prescription Drug User Fee Act (PDUFA) on 6 April 2018. European Medicines Agency (EMA) approval in the same setting is awaited. The possibility of using PARP inhibitors as a maintenance therapy, as a front-line therapy to combat recurrence, and in combination with anti-angiogenic agents and immune-therapies appears to be of particular interest.
大约 50%的高级别浆液性卵巢癌存在同源重组（HR）途径相关缺陷。PARP 抑制剂可阻止单链 DNA 损伤修复，并促使缺陷向双链断裂发展，从而导致所谓的“合成致死”。涵盖领域：在这篇综述中，作者讨论了鲁卡帕尼作为单一药物或维持治疗卵巢癌的疗效和毒性。这包括 NGS Foundation Medicine 对该药物在卵巢癌治疗算法中的作用的评估。此外，还介绍了该药物未来发展的前景。专家意见：美国食品和药物管理局（FDA）已批准该药物用于治疗至少接受过两种化疗的复发性 BRCA 突变卵巢癌，并且已根据处方药用户收费法（PDUFA）于 2018 年 4 月 6 日接受了该药物用于对铂类化疗有反应的患者的维持治疗的补充新药申请。正在等待欧洲药品管理局（EMA）在相同情况下的批准。PARP 抑制剂作为维持治疗、作为预防复发的一线治疗、以及与抗血管生成药物和免疫疗法联合使用的可能性似乎特别令人感兴趣。
