HonorHealth Research Institute, Phoenix, Arizona, USA
University of Arizona College of Medicine, Phoenix, Arizona, USA.
Int J Gynecol Cancer. 2023 Jun 5;33(6):971-981. doi: 10.1136/ijgc-2022-004079.
Niraparib is a poly (ADP-ribose) polymerase inhibitor that has shown a significant improvement in progression-free survival irrespective of biomarker status in patients with advanced epithelial ovarian cancer. This review focuses on the adverse events associated with niraparib and their management to maintain efficacy of niraparib treatment and improve quality of life for patients. In five trials assessing efficacy of niraparib in patients with advanced epithelial ovarian cancer (PRIMA, NOVA, NORA, QUADRA, and PRIME), treatment-emergent adverse events of any grade were reported in nearly all patients (≥99%) receiving niraparib; the events were grade ≥3 in 51-74% of patients. Across all lines of therapy, treatment-emergent adverse events led to dose interruptions in 62-80% of patients receiving niraparib and dose reductions in 47-71%. Hematologic events were most frequently reported, including thrombocytopenia, anemia, and neutropenia. Common non-hematologic events included gastrointestinal events, which were generally low grade (<5% were grade ≥3). Clinical strategies to manage these and other events, such as fatigue and insomnia, cognitive behavioral therapy and pharmacologic agents, are summarized. Once-daily niraparib dosing may be advantageous for some patients for many reasons, including night-time dosing which may help alleviate gastrointestinal symptoms. An individualized starting dose (determined by baseline body weight and platelet count) of niraparib demonstrated an improved safety profile while maintaining efficacy. Patients receiving the niraparib individualized starting dose had fewer grade ≥3 adverse events, dose interruptions, and dose reductions than patients receiving a fixed starting dose. The safety profile of niraparib across five pivotal studies in advanced epithelial ovarian cancer was consistent across multiple lines of treatment, including as maintenance therapy in first-line and recurrent settings and as treatment in heavily pre-treated patients. Long-term safety data from the NOVA trial confirmed that, with appropriate and early dose modifications, niraparib is well tolerated.
尼拉帕利是一种聚（ADP-核糖）聚合酶抑制剂，无论生物标志物状态如何，在晚期上皮性卵巢癌患者中均显著改善了无进展生存期。本综述重点介绍了尼拉帕利相关的不良反应及其管理，以维持尼拉帕利治疗的疗效并提高患者的生活质量。在五项评估尼拉帕利在晚期上皮性卵巢癌患者中的疗效的试验（PRIMA、NOVA、NORA、QUADRA 和 PRIME）中，接受尼拉帕利治疗的几乎所有患者（≥99%）均报告了治疗出现的任何级别不良反应；≥3 级不良反应的患者占 51-74%。在所有治疗线中，接受尼拉帕利治疗的患者中有 62-80%因治疗出现的不良反应而中断剂量，47-71%的患者减少剂量。最常报告的是血液学事件，包括血小板减少症、贫血和中性粒细胞减少症。常见的非血液学事件包括胃肠道事件，这些事件通常为低级别（<5%为≥3 级）。总结了管理这些和其他事件（如疲劳和失眠）的临床策略，包括认知行为疗法和药物治疗。由于许多原因，包括夜间给药可能有助于缓解胃肠道症状，每日一次的尼拉帕利给药可能对某些患者有利。尼拉帕利的起始剂量个体化（根据基线体重和血小板计数确定）在保持疗效的同时显示出更好的安全性。与接受固定起始剂量的患者相比，接受尼拉帕利个体化起始剂量的患者发生≥3 级不良反应、剂量中断和剂量减少的情况更少。尼拉帕利在晚期上皮性卵巢癌的五项关键性研究中的安全性特征在多种治疗线中是一致的，包括一线和复发性治疗中的维持治疗以及在重度预处理患者中的治疗。NOVA 试验的长期安全性数据证实，通过适当和早期的剂量调整，尼拉帕利具有良好的耐受性。
