Risk of secondary myelodysplastic syndromes and acute myeloid leukaemia following poly(ADP-ribose) polymerase inhibitor treatment for advanced-stage recurrent ovarian cancer: A retrospective cohort study in England

IF 7.6 1区医学 Q1 ONCOLOGY

European Journal of Cancer Pub Date : 2025-04-25 DOI:10.1016/j.ejca.2025.115472

Luke Steventon , Shibani Nicum , Pinkie Chambers , Kenneth Man , David Dodwell , Zhe Wang , Apini Patel , Ben Pickwell-Smith , Li Wei

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引用次数: 0

Abstract

Background

Poly(ADP-ribose) polymerase inhibitors (PARPi) maintenance therapies are used to treat advanced ovarian cancer in first line and recurrent settings. Because of concerns about associations between PARPi therapy and secondary cancers myelodysplastic syndrome (MDS) and acute myeloid leukaemia (AML), a meta-analysis of clinical trials was conducted, reporting MDS/AML incidence of 0.73 %; however, clinical trial populations are highly selective and may not reflect incidence in the wider population.

Methods

This retrospective cohort study calculated incidence of MDS/AML within five years of completing first-line chemotherapy + /- PARPi maintenance for recurrent, advanced-stage ovarian cancer. Absolute and relative risks were calculated and compared to meta-analysis.

Results

Of 11,531 included patients, 1529 received PARPi and 10,002 chemotherapy only. Absolute risk of MDS/AML was 0.3 % (n = 5/1529) for chemotherapy + PARPi maintenance therapy versus 0.1 % (n = 10/10,002) for chemotherapy alone. Relative risk was 2.97 (95 % CI 1.02, 8.68, p = 0.046) in patients receiving PARPi maintenance versus chemotherapy alone.

Discussion

Relative risk of MDS/AML was greater in patients treated with PARPi; however, absolute risk was low in both treatment groups and lower than in the meta-analysis of trials. This analysis suggests small increased relative risk of MDS/AML associated with PARPi maintenance versus chemotherapy only, but not increased absolute risk.

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英国的一项回顾性队列研究：晚期复发性卵巢癌的聚（adp -核糖）聚合酶抑制剂治疗后继发性骨髓增生异常综合征和急性髓性白血病的风险

背景：聚（adp -核糖）聚合酶抑制剂（PARPi）维持疗法用于治疗晚期卵巢癌的一线和复发设置。由于担心PARPi治疗与继发性癌症骨髓增生异常综合征（MDS）和急性髓性白血病（AML）之间的关联，进行了一项临床试验的荟萃分析，报告MDS/AML发病率为0.73 %；然而，临床试验人群是高度选择性的，可能不能反映更广泛人群的发病率。方法：本回顾性队列研究计算复发性晚期卵巢癌患者在完成一线化疗+ /- PARPi维持后5年内MDS/AML的发生率。计算绝对风险和相对风险，并与meta分析进行比较。结果11,531例患者中，1529例接受PARPi治疗，10,002例仅接受化疗。化疗+ PARPi维持治疗的MDS/AML绝对风险为0.3 % (n = 5/1529)，而单独化疗的绝对风险为0.1 % （n = 10/ 1002）。与单纯化疗相比，接受PARPi维持治疗的患者相对风险为2.97（95 % CI 1.02, 8.68, p = 0.046）。PARPi治疗的患者发生MDS/AML的相对风险更高；然而，两个治疗组的绝对风险都很低，低于试验的荟萃分析。该分析表明，与仅化疗相比，维持PARPi与MDS/AML相关的相对风险增加较小，但绝对风险没有增加。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

European Journal of Cancer 医学-肿瘤学

CiteScore

11.50

自引率

4.80%

发文量

953

审稿时长

23 days

期刊介绍： The European Journal of Cancer (EJC) serves as a comprehensive platform integrating preclinical, digital, translational, and clinical research across the spectrum of cancer. From epidemiology, carcinogenesis, and biology to groundbreaking innovations in cancer treatment and patient care, the journal covers a wide array of topics. We publish original research, reviews, previews, editorial comments, and correspondence, fostering dialogue and advancement in the fight against cancer. Join us in our mission to drive progress and improve outcomes in cancer research and patient care.