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尼拉帕利用于治疗卵巢癌。

Niraparib for the treatment of ovarian cancer.

作者信息

Kanjanapan Yada, Lheureux Stephanie, Oza Amit M

机构信息

a Division of Medical Oncology and Hematology, Department of Medicine, Princess Margaret Cancer Centre , University of Toronto , Toronto , Canada.

出版信息

Expert Opin Pharmacother. 2017 Apr;18(6):631-640. doi: 10.1080/14656566.2017.1297423. Epub 2017 Apr 7.

Abstract

Poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitors are being developed in maintenance and recurrence treatment settings in ovarian cancer. They inhibit single-stranded DNA repair, inducing synthetic lethality in cells with underlying homologous recombination deficiency (HRD). Marked responses are seen in ovarian cancers with breast cancer gene 1 (BRCA1) or 2 (BRCA2) mutation, although up to 50% of high-grade serous ovarian cancers (HGSOC) have HRD may also benefit. Areas covered: This review focuses on niraparib (oral PARP I and II inhibitor), its clinical testing in ovarian cancer, including the Myriad MyChoice HRD test as a potential companion diagnostic. Future directions plus ongoing trials, including novel combinations are highlighted. Expert opinion: There is now level 1 evidence of efficacy from the first randomized placebo-controlled phase III trial using niraparib maintenance in women with platinum-sensitive recurrent HGSOC with complete or partial response post platinum-based chemotherapy. Niraparib improved progression free survival over placebo in all groups of women. The benefit was greatest in patients with germline BRCA1/2 mutation, followed by HRD positive tumors; however, absence of either does not exclude the possibility of benefit from niraparib maintenance. Additional studies are underway with niraparib in the first line maintenance, and 4/5 line recurrence treatment settings.

摘要

聚(腺苷二磷酸核糖)聚合酶(PARP)抑制剂正在卵巢癌的维持治疗和复发治疗中进行研发。它们抑制单链DNA修复,在存在潜在同源重组缺陷(HRD)的细胞中诱导合成致死。在患有乳腺癌基因1(BRCA1)或2(BRCA2)突变的卵巢癌中可见显著反应,尽管高达50%的高级别浆液性卵巢癌(HGSOC)存在HRD也可能从中获益。涵盖领域:本综述重点关注尼拉帕利(口服PARP I和II抑制剂),其在卵巢癌中的临床试验,包括作为潜在伴随诊断的Myriad MyChoice HRD检测。强调了未来方向以及正在进行的试验,包括新的联合用药。专家观点:在铂敏感复发HGSOC且铂类化疗后有完全或部分缓解的女性中,使用尼拉帕利维持治疗的首个随机安慰剂对照III期试验已有1级疗效证据。尼拉帕利在所有女性组中均改善了无进展生存期。在胚系BRCA1/2突变患者中获益最大,其次是HRD阳性肿瘤;然而,两者均不存在并不排除从尼拉帕利维持治疗中获益的可能性。尼拉帕利在一线维持治疗以及4/5线复发治疗中的其他研究正在进行中。

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