Background: Soft tissue sarcomas (STS) are aggressive cancers that show increasing response to novel targeted-therapies and immune-checkpoint-inhibitors. Despite anecdotal reports of cardiovascular adverse events (AEs) and major adverse cardiovascular events (MACE) potentially hindering their utility, the true cardiotoxic profile of these novel-therapies in STS has been largely understudied.Methods: We assessed the incidence and severity of AEs and MACE of contemporary FDA-approved targeted and immune-based therapies for STS, using data from landmark clinical trials supporting FDA-approval. We also analyzed data from the FDA adverse-event-reporting-system-(FAERS) for FDA-approved STS targeted and immune-based therapies for comparative real-world validation.Results: Overall, 12 clinical trials supporting FDA-approval of STS targeted-therapies and immune-checkpoint-inhibitors, incorporating 1249 patients, were identified. These clinical trials revealed 751 AEs including, hypertension (382, 50.87%), atrial fibrillation (3, 0.40%), myocardial infarction (2, 0.27%), cardiac failure (congestive included) (9, 1.20%), and cardiac failure (heart failure included) (7, 0.93%). Compared to placebo, those treated saw higher MACE (OR: 3.27,p< 0.001). The FAERS data showed 489 reported AEs including hypertension (275, 56.24%), atrial fibrillation (31, 6.34%), myocardial infarction (15, 3.07%), and cardiac failure (congestive included) (30, 6.13%). Programmed death-ligand 1 (PD-L1) inhibitors had the highest probability of AEs (0.65, 1.17), followed by tyrosine kinase inhibitors (0.66, 0.11), tropomyosin receptor kinase inhibitors (0.25, 0.13), mammalian target of rapamycin inhibitors (0.21, 0.09), and enhancer of zeste homologue 2 inhibitors (0.11, 0.06). Proportions were calculated from the samples in clinical trials supporting FDA-approval and FAERS, respectively.Conclusions: In this investigation, contemporary FDA-approved therapies for STS are associated with increased risk of AEs
背景：软组织肉瘤（STS）是一种侵袭性癌症，对新型靶向治疗和免疫检查点抑制剂的反应日益增强。尽管有零星报道指出心血管不良事件（AEs）和主要不良心血管事件（MACE）可能影响这些疗法的应用，但这些新型疗法在STS中的真实心脏毒性特征在很大程度上尚未得到充分研究。 方法：我们利用支持FDA批准的关键临床试验数据，评估了当前FDA批准的STS靶向治疗和免疫疗法的AEs和MACE的发生率及严重程度。同时，我们还分析了FDA不良事件报告系统（FAERS）中关于FDA批准的STS靶向治疗和免疫疗法的数据，以进行现实世界的比较验证。 结果：共确定了12项支持FDA批准STS靶向治疗和免疫检查点抑制剂的临床试验，涉及1249名患者。这些临床试验报告了751例AEs，包括高血压（382例，50.87%）、心房颤动（3例，0.40%）、心肌梗死（2例，0.27%）、心力衰竭（包括充血性心力衰竭）（9例，1.20%）和心力衰竭（包括心衰）（7例，0.93%）。与安慰剂组相比，接受治疗的患者MACE发生率更高（OR：3.27，p < 0.001）。FAERS数据显示了489例报告的AEs，包括高血压（275例，56.24%）、心房颤动（31例，6.34%）、心肌梗死（15例，3.07%）和心力衰竭（包括充血性心力衰竭）（30例，6.13%）。程序性死亡配体1（PD-L1）抑制剂的AEs发生概率最高（0.65，1.17），其次是酪氨酸激酶抑制剂（0.66，0.11）、原肌球蛋白受体激酶抑制剂（0.25，0.13）、哺乳动物雷帕霉素靶蛋白抑制剂（0.21，0.09）和zeste同源物2增强子抑制剂（0.11，0.06）。比例分别根据支持FDA批准的临床试验样本和FAERS数据计算得出。 结论：本研究表明，当前FDA批准的STS疗法与AEs风险增加相关。
肿瘤(癌症)患者之家