PARP抑制剂在实体瘤中的血液学毒性:一项系统综述和安全性荟萃分析。

Hematological toxicity of parp inhibitors in solid tumors: a systematic review and safety meta-analysis.

作者信息

Maiorano Brigida Anna, Catalano Martina, Maiorano Mauro Francesco Pio, Signori Alessio, Loizzi Vera, Cormio Gennaro, Reni Michele, Roviello Giandomenico, Necchi Andrea

机构信息

Department of Medical Oncology, IRCCS San Raffaele Hospital, Milan, Italy.

Department of Health Sciences, Section of Clinical Pharmacology and Oncology, University of Florence, Florence, Italy.

出版信息

Cancer Metastasis Rev. 2025 Aug 14;44(3):65. doi: 10.1007/s10555-025-10283-1.

Abstract

Poly (ADP-ribose) polymerase (PARP) inhibitors (PARPis) are effective agents in different tumor types. A typical class of adverse events (AEs) associated with these agents, often leading to treatment modifications and discontinuations of treatment, is hematological toxicity. In our systematic review and safety meta-analysis, we investigated the incidence and risk of all grades and ≥ grade (G) 3 hematological AEs, including anemia, neutropenia, thrombocytopenia, and acute myeloid leukemia (AML)/myelodysplastic syndrome (MDS) due to PARPis, used alone or in combination, in patients diagnosed with solid tumors. This systematic review and meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement. We systematically searched the PubMed, EMBASE, and Cochrane databases, the American Society of Clinical Oncology, and the European Society of Medical Oncology meeting abstracts for randomized clinical trials (RCTs) concerning the use of PARPis in patients with solid tumors. The search deadline was April 30, 2024. We calculated risk ratios (RRs) for all-grade and ≥ G3 AEs of PARPis versus non-PARPis. 31 phase II/III RCTs were included. Anemia was the most common all-grade (49.2%) and ≥ G3 AE (25.0%). The administration of PARPis significantly increased the risk of developing all grades of anemia (RR = 2.15, p < 0.00001), neutropenia (RR = 1.50, p = 0.0002), and thrombocytopenia (RR = 2.59, p < 0.00001) compared to non-PARPis. Similarly, a significant increase in the risk of ≥ G3 anemia (RR = 5.43, p < 0.00001), neutropenia (RR = 1.70, p = 0.002), and thrombocytopenia (RR = 5.42, p < 0.00001) was detected. PARPis did not increase the risk of AML/MDS (p = 0.86). PARPis increase the risk of hematologic toxicity compared to other treatments in solid tumors. Clinicians should be aware of this risk, especially given the expected increase in PARPis use in the next year in different tumor types.

摘要

聚(ADP - 核糖)聚合酶(PARP)抑制剂(PARPis)是治疗不同肿瘤类型的有效药物。与这些药物相关的一类典型不良事件(AEs)是血液学毒性,这常常导致治疗调整和治疗中断。在我们的系统评价和安全性荟萃分析中,我们调查了单独或联合使用PARPis的实体瘤患者中,所有级别及≥3级(G3)血液学不良事件的发生率和风险,这些不良事件包括贫血、中性粒细胞减少、血小板减少以及急性髓系白血病(AML)/骨髓增生异常综合征(MDS)。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。我们系统检索了PubMed、EMBASE和Cochrane数据库、美国临床肿瘤学会以及欧洲医学肿瘤学会会议摘要,以查找关于PARPis在实体瘤患者中应用的随机临床试验(RCTs)。检索截止日期为2024年4月30日。我们计算了PARPis与非PARPis相比,所有级别及≥G3不良事件的风险比(RRs)。纳入了31项II/III期RCTs。贫血是最常见的所有级别(49.2%)及≥G3不良事件(25.0%)。与非PARPis相比,PARPis的使用显著增加了发生所有级别贫血(RR = 2.15,p < 0.00001)、中性粒细胞减少(RR = 1.50,p = 0.0002)和血小板减少(RR = 2.59,p < 0.00001)的风险。同样,≥G3贫血(RR = 5.43,p < 0.00001)、中性粒细胞减少(RR = 1.70,p = 0.002)和血小板减少(RR = 5.42,p < 0.00001)的风险也显著增加。PARPis并未增加AML/MDS的风险(p = 0.86)。与实体瘤的其他治疗方法相比,PARPis增加了血液学毒性的风险。临床医生应意识到这种风险,特别是考虑到预计明年不同肿瘤类型中PARPis的使用将会增加。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f254/12350551/f1b87ddd601f/10555_2025_10283_Fig1_HTML.jpg

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