Department of Obstetrics and Gynecology, Sanggye Paik Hospital, Inje University College of Medicine, Seoul, 01757, Republic of Korea.
Department of Statistics, College of Natural Science, University of Seoul, Seoul, 02504, Republic of Korea.
Target Oncol. 2024 Mar;19(2):251-262. doi: 10.1007/s11523-024-01037-0. Epub 2024 Feb 28.
Despite improvement in progression-free survival (PFS) with poly (ADP-ribose) polymerase (PARP) inhibitors (PARPi) as maintenance treatment for patients with epithelial ovarian cancer (EOC), a comparative analysis of clinical events of interest (CEIs) of different PARPi is scarce.
This study aimed to compare the safety of different PARPi in patients with EOC.
Through analyzing the Korean National Health Insurance Service from January 2009 to January 2022, this study involved BRCA-mutated, platinum-sensitive patients with EOC treated with olaparib (tablet), niraparib, and olaparib (capsule) as first-line or second-line maintenance treatment. CEIs were identified using International Statistical Classification of Diseases (ICD) 9/10 codes, with additional outcomes being dose modification and persistence.
In the first-line maintenance treatment [118 niraparib, 104 olaparib (tablet) patients], no significant differences were noted in CEIs, dose reduction, or 6-month discontinuation rate. For second-line maintenance treatment [303 niraparib, 126 olaparib (tablet), and 675 olaparib (capsule) patients], niraparib was associated with a higher risk of hematologic CEIs, particularly anemia, compared with olaparib (tablet) (0.51 [0.26-0.98] and 0.09 [0.01-0.74], respectively), and higher rate of discontinuation rate at 6 months. Of note, patients over 60 years old showed an increased risk of CEIs with niraparib, as indicated by the hazard ratio divergence in restricted cubic spline plots.
No differences were observed among the PARPi during first-line maintenance treatment. However, in the second-line maintenance treatment, significant differences were observed in the risk of experiencing CEIs, dose alteration possibilities, and discontinuation of PARPi between niraparib and olaparib (tablets). Moreover, our findings suggest that an age of 60 years may be a critical factor in selecting PARPi to reduce CEI incidence.
尽管聚（ADP-核糖）聚合酶（PARP）抑制剂（PARPi）作为上皮性卵巢癌（EOC）患者的维持治疗可改善无进展生存期（PFS），但不同 PARPi 的临床关注事件（CEI）的比较分析仍很少见。
本研究旨在比较 EOC 患者中不同 PARPi 的安全性。
通过分析 2009 年 1 月至 2022 年 1 月期间的韩国国家健康保险服务数据，本研究纳入了接受奥拉帕利（片剂）、尼拉帕利和奥拉帕利（胶囊）一线或二线维持治疗的 BRCA 突变、铂类敏感的 EOC 患者。CEI 使用国际疾病分类（ICD）9/10 代码确定，并对剂量调整和持续用药进行了额外的评估。
在一线维持治疗（118 例尼拉帕利、104 例奥拉帕利（片剂）患者）中，CEI、剂量减少或 6 个月停药率无显著差异。对于二线维持治疗（303 例尼拉帕利、126 例奥拉帕利（片剂）和 675 例奥拉帕利（胶囊）患者），与奥拉帕利（片剂）相比，尼拉帕利与血液学 CEI 相关的风险更高，特别是贫血（0.51[0.26-0.98]和 0.09[0.01-0.74]），6 个月时停药率更高。值得注意的是，年龄在 60 岁以上的患者使用尼拉帕利时 CEI 的风险增加，限制立方样条图的风险比发散表明了这一点。
在一线维持治疗中，PARPi 之间未观察到差异。然而，在二线维持治疗中，尼拉帕利和奥拉帕利（片剂）之间在 CEI 风险、剂量调整可能性和 PARPi 停药方面存在显著差异。此外，我们的研究结果表明，年龄 60 岁可能是选择 PARPi 以降低 CEI 发生率的一个关键因素。
