PARP抑制剂治疗转移性去势抵抗性前列腺癌患者血栓栓塞和心血管不良事件的发生率和风险：系统回顾和安全性荟萃分析

IF 3.2 3区医学 Q1 UROLOGY & NEPHROLOGY

European Urology Open Science Pub Date : 2025-02-01 DOI:10.1016/j.euros.2024.12.008

Brigida Anna Maiorano , Martina Catalano , Chiara Mercinelli , Antonio Cigliola , Valentina Tateo , Neeraj Agarwal , Shilpa Gupta , Giandomenico Roviello , Andrea Necchi

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引用次数: 0

摘要

背景与目的：PARP抑制剂（PARPi）治疗是转移性去势抵抗性前列腺癌（mCRPC）患者的有效选择。由于心血管和血栓栓塞不良事件（ae）并不常见，关于这些药物在mCRPC中心血管和血栓栓塞安全性的数据很少。我们的目的是分析PARPi治疗mCRPC患者的主要不良心血管事件（mace）、血栓栓塞事件和高血压的发生率和风险。方法：我们按照系统评价和荟萃分析首选报告项目（PRISMA）声明进行了系统评价和荟萃分析。截至2024年3月31日，我们系统地检索了PubMed、EMBASE和Cochrane数据库以及美国临床肿瘤学会和欧洲医学肿瘤学会会议摘要，以获取PARPi用于mCRPC的临床试验。我们分析了所有级别和高级别mace、血栓栓塞事件和高血压的合并发生率，并计算了PARPi与非PARPi治疗的风险比（rr）。主要发现和局限性：我们在meta分析中纳入了11项2期或3期试验。在任何级别（17.2%）和高级别（9.3%）事件中，高血压是最常见的AE。与其他治疗相比，PARPi与高级别mace的风险显著升高相关(RR 2.03；p = 0.03)和血栓栓塞事件(RR 2.15；p = 0.002)，尤其是静脉血栓栓塞(VTE；RR 2.13;p = 0.004)和肺栓塞(RR 3.60；p = 0.001)。除静脉血栓栓塞外，高血压、任何级别mace和血栓栓塞性ae的风险均未显著升高(RR 2.17；p = 0.01)。结论和临床意义：与mCRPC的其他治疗相比，PARPi的使用有更高的心血管和血栓栓塞毒性风险，尽管这些毒性很少见。临床医生应该意识到这种风险，特别是在经常有合并症和伴随治疗的人群中，以便正确监测和管理这些不良事件。患者总结：被称为PARP抑制剂的药物在治疗对激素治疗无效的转移性前列腺癌方面非常有效。然而，它们的使用与一些心血管不良事件有关，尽管这些事件很少见。我们的研究表明，与其他治疗相比，PARP抑制剂似乎更容易发生这些事件，特别是对于严重级别的患者。医生和患者应该意识到这种风险，以帮助预防、识别和管理这些罕见并发症的发生。

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Incidence and Risk of Thromboembolic and Cardiovascular Adverse Events with PARP Inhibitor Treatment in Patients with Metastatic Castration-resistant Prostate Cancer: A Systematic Review and Safety Meta-analysis

Background and objective

PARP inhibitor (PARPi) treatment is an effective option for patients with metastatic castration-resistant prostate cancer (mCRPC). There are few data on the cardiovascular and thromboembolic safety of these agents in mCRPC, as cardiovascular and thromboembolic adverse events (AEs) are uncommon. Our aim was to analyze the incidence and risk of major adverse cardiovascular events (MACEs), thromboembolic events, and hypertension with PARPi therapy in mCRPC.

Methods

We conducted a systematic review and meta-analysis in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. We systematically searched the PubMed, EMBASE, and Cochrane databases and the American Society of Clinical Oncology and European Society of Medical Oncology meeting abstracts for clinical trials on PARPi use in mCRPC up to March 31, 2024. We analyzed the pooled incidence of all-grade and high-grade MACEs, thromboembolic events, and hypertension, and calculated risk ratios (RRs) for PARPi versus non-PARPi treatment.

Key findings and limitations

We included 11 phase 2 or 3 trials in our meta-analysis. Hypertension was the most common AE for both any-grade (17.2%) and high-grade (9.3%) events. In comparison to other treatments, PARPi was associated with significantly higher risk of high-grade MACEs (RR 2.03; p = 0.03) and thromboembolic events (RR 2.15; p = 0.002), especially venous thromboembolism (VTE; RR 2.13; p = 0.004) and pulmonary embolism (RR 3.60; p = 0.001). The risk of hypertension, any-grade MACEs, and thromboembolic AEs was not significantly higher, apart from VTE (RR 2.17; p = 0.01).

Conclusions and clinical implications

There is higher risk of high-grade cardiovascular and thromboembolic toxicity with PARPi use in comparison to other treatments in mCRPC, although these toxicities are rare. Clinicians should be aware of this risk, especially in a population that often has comorbidities and concomitant treatments, for correct monitoring and management of these AEs.

Patient summary

Drugs called PARP inhibitors are very effective in the treatment of metastatic prostate cancer that does not respond to hormone treatment. However, their use is associated with some cardiovascular adverse events, although these are rare. Our study shows that these events seem to be more frequent with PARP inhibitors than with other treatments, especially for severe grades. Doctors and patients should be aware of this risk to help in preventing, recognizing, and managing the occurrence of these rare complications.

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