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PARP抑制剂在晚期卵巢癌中的血液学毒性:一项系统评价和荟萃分析。

Haematological toxicity of PARP inhibitors in advanced ovarian cancer: A systematic review and meta-analysis.

作者信息

Pio Maiorano Mauro Francesco, Loizzi Vera, Maiorano Brigida Anna, Cormio Gennaro

机构信息

Department of Interdisciplinary Medicine, University of Bari 'Aldo Moro', Bari, Italy.

Department of Interdisciplinary Medicine, University of Bari 'Aldo Moro', Bari, Italy; Gynaecologic Oncology Unit, IRCCS Istituto Tumori 'Giovanni Paolo II', Bari, Italy.

出版信息

Eur J Obstet Gynecol Reprod Biol. 2025 Feb;305:232-240. doi: 10.1016/j.ejogrb.2024.12.021. Epub 2024 Dec 15.

Abstract

BACKGROUND

Poly (ADP-ribose) polymerase inhibitors (PARPis) are effective treatment options for patients with advanced ovarian cancer (OC). A typical adverse event (AE) of these agents is haematological toxicity, which represents the leading cause of treatment modification and discontinuation. This systematic review and meta-analysis aimed to analyse the risk of haematological AEs, including anaemia, neutropenia and thrombocytopenia due to the use of PARPis in patients with OC.

METHODS

This systematic review and meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement. PubMed, EMBASE and Cochrane databases, and international meeting abstracts were searched systematically for clinical trials concerning the use of PARPis in patients with OC. The search deadline was 30 March 2024. The pooled incidence of all grades and grade 3or more (≥G3) anaemia, neutropenia and thrombocytopenia were analysed. Subsequently, risk ratios (RRs) were calculated for all grades and ≥G3 AEs of PARPis compared with non-PARPis from randomized controlled trials.

RESULTS

In total, 12 phase II/III trials with olaparib, niraparib and rucaparib were included in this study. Anaemia was the most common all grade (28.8 %) and ≥G3 (12.1 %) AE. The administration of PARPis increased the risk of developing all grade anaemia [risk ratio (RR) = 2.44], neutropenia (RR = 3.15) and thrombocytopenia (RR = 4.66) significantly compared with non-PARPis. Similarly, a significant increase in the risk of ≥G3 anaemia (RR = 5.73) and thrombocytopenia (RR = 5.44), and a non-significant increase in the risk of neutropenia (RR = 3.41) were detected.

CONCLUSIONS

In patients with advanced OC, PARPis increase the risk of haematological toxicity compared with other treatments (high-quality evidence). Clinicians should be aware of this risk and the correct management, as these drugs are highly employed in these patients.

摘要

背景

聚(ADP - 核糖)聚合酶抑制剂(PARPis)是晚期卵巢癌(OC)患者的有效治疗选择。这些药物的一种典型不良事件(AE)是血液学毒性,这是治疗调整和停药的主要原因。本系统评价和荟萃分析旨在分析因OC患者使用PARPis导致的血液学AE风险,包括贫血、中性粒细胞减少和血小板减少。

方法

本系统评价和荟萃分析遵循系统评价和荟萃分析的首选报告项目(PRISMA)声明。系统检索了PubMed、EMBASE和Cochrane数据库以及国际会议摘要,以查找关于OC患者使用PARPis的临床试验。检索截止日期为2024年3月30日。分析了所有级别以及3级或更高级别(≥G3)贫血、中性粒细胞减少和血小板减少的合并发生率。随后,计算了PARPis与随机对照试验中的非PARPis相比,所有级别和≥G3 AE的风险比(RRs)。

结果

本研究共纳入了12项使用奥拉帕尼、尼拉帕尼和鲁卡帕尼的II/III期试验。贫血是最常见的所有级别(28.8%)和≥G3(12.1%)AE。与非PARPis相比,PARPis的使用显著增加了发生所有级别贫血[风险比(RR) = 2.44]、中性粒细胞减少(RR = 3.15)和血小板减少(RR = 4.66)的风险。同样,检测到≥G3贫血(RR = 5.73)和血小板减少(RR = 5.44)的风险显著增加,中性粒细胞减少风险有非显著增加(RR = 3.41)。

结论

在晚期OC患者中,与其他治疗相比,PARPis增加了血液学毒性风险(高质量证据)。临床医生应意识到这种风险并进行正确管理,因为这些药物在这些患者中广泛使用。

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