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阿贝西单抗用于癌症相关血栓形成:在正确的时间为正确的目的使用正确的药物。全面综述。

Abelacimab in Cancer-Associated Thrombosis: The Right Drug at the Right Time for the Right Purpose. A Comprehensive Review.

作者信息

Fioretti Agnese Maria, Leopizzi Tiziana, La Forgia Daniele, De Luca Raffaele, Oreste Donato, Inchingolo Riccardo, Scicchitano Pietro, Oliva Stefano

机构信息

Cardio-Oncology Unit, IRCCS Istituto Tumori "Giovanni Paolo II", 70124 Bari, Italy.

Cardiology-Intensive Care Unit, Ospedale SS. Annunziata, 74121 Taranto, Italy.

出版信息

Rev Cardiovasc Med. 2023 Oct 19;24(10):295. doi: 10.31083/j.rcm2410295. eCollection 2023 Oct.

Abstract

Cancer-associated thrombosis (CAT) is a devastating complication of cancer that can significantly impact a patient's health and life. The incidence of CAT is approximately 20%, and 1 in 5 cancer patients will develop CAT annually. Indeed, CAT can promote pulmonary embolism and deep vein thrombosis, leading to increased morbidity and mortality that dramatically impact survival. CAT can also provoke delay or discontinuation of anticancer treatment, which may result in a lack of treatment efficacy and high costs for patients, institutions, and society. Current guidelines advocate direct oral anticoagulants (DOACs) as the first-line anticoagulant option in CAT. Compared to low-molecular-weight-heparins (LMWHs), DOACs are advantageous in that they typically have an oral route of administration, do not require laboratory monitoring, and have a more predictable anticoagulant effect. However, in patients with thrombocytopenia, renal failure, or those receiving anticancer regimens with potential for drug-drug interactions, LMWH is still the mainstay of care. The main limitation of current anticoagulant agents is related to bleeding risk (BR), both for DOACs and LMWHs. Specifically, DOACs have been associated with high BR in gastrointestinal and genitourinary cancers. In this challenging scenario, abelacimab, an anti-factor XI agent, could represent a viable option in the management of CAT due to its "hemostasis sparing" effect. The safe profile of abelacimab could be useful in patients with active malignancy and CAT, as long-term anticoagulant therapy is often required. Two ongoing international phase III trials (Aster and Magnolia) compare abelacimab with the standard of care (i.e., apixaban in patients with CAT and dalteparin in those with CAT and high BR, respectively). Abelacimab is a new and attractive anticoagulant for the management of CAT, especially in the insidious and critical scenario of active cancer patients with venous thromboembolism and high BR. The aim of this narrative review is to discuss the updated evidence on the performance of DOACs and LMWHs in the treatment of CAT and to focus on the potential role of abelacimab in CAT and its promising associated clinical trials.

摘要

癌症相关血栓形成(CAT)是癌症的一种严重并发症,会对患者的健康和生活产生重大影响。CAT的发病率约为20%,每5名癌症患者中就有1人每年会发生CAT。事实上,CAT会引发肺栓塞和深静脉血栓形成,导致发病率和死亡率增加,对生存率产生显著影响。CAT还可能导致抗癌治疗延迟或中断,这可能会导致治疗效果不佳,给患者、机构和社会带来高昂成本。目前的指南提倡将直接口服抗凝剂(DOACs)作为CAT的一线抗凝选择。与低分子肝素(LMWHs)相比,DOACs的优势在于其通常采用口服给药途径,无需实验室监测,且抗凝效果更可预测。然而,在血小板减少症、肾衰竭患者或接受可能存在药物相互作用的抗癌方案的患者中,LMWH仍是主要的治疗药物。目前抗凝剂的主要局限性与出血风险(BR)有关,DOACs和LMWHs均如此。具体而言,DOACs与胃肠道和泌尿生殖系统癌症的高BR相关。在这种具有挑战性的情况下,抗因子XI药物阿贝西单抗因其“保留止血”作用,可能是CAT管理中的一个可行选择。阿贝西单抗的安全性特征对于患有活动性恶性肿瘤和CAT的患者可能有用,因为通常需要长期抗凝治疗。两项正在进行的国际III期试验(Aster和Magnolia)分别将阿贝西单抗与标准治疗方法进行比较(即CAT患者使用阿哌沙班,CAT且BR高的患者使用达肝素)。阿贝西单抗是一种用于CAT管理的新型且有吸引力的抗凝剂,特别是在患有静脉血栓栓塞和高BR的活动性癌症患者这种隐匿且危急的情况下。本叙述性综述的目的是讨论DOACs和LMWHs在CAT治疗中表现的最新证据,并关注阿贝西单抗在CAT中的潜在作用及其前景广阔的相关临床试验。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7474/11262452/1fbaf717e169/2153-8174-24-10-295-g1.jpg

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