Jang Sekwon, Zheng Chaoyi, Tsai Huei-Ting, Fu Alex Z, Barac Ana, Atkins Michael B, Freedman Andrew N, Minasian Lori, Potosky Arnold L
Division of Oncology, Inova Dwight and Martha Schar Cancer Institute, Fairfax, Virginia.
Department of Biostatistics, Bioinformatics, and Biomathematics, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC.
Cancer. 2016 Jan 1;122(1):124-30. doi: 10.1002/cncr.29728. Epub 2015 Oct 6.
Sorafenib and sunitinib are oral vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors (TKIs) approved in 2005 and 2006, respectively, for the treatment of patients with renal cell carcinoma (RCC). A population-based, observational cohort study of the cardiovascular risk of VEGFR TKI therapy in elderly RCC patients was conducted.
Using the Surveillance, Epidemiology, and End Results-Medicare database, this study analyzed patients who were 66 years old or older and were diagnosed with RCC from 2000 to 2009. The incidence of cardiovascular adverse events, including congestive heart failure and cardiomyopathy (CHF/CM), acute myocardial infarction (AMI), stroke, and cardiovascular deaths, was examined through December 2010. A Cox proportional hazards model was created to calculate the hazard ratio (HR), and adjustments were made for age, sex, comorbidity, and the use of other systemic therapy.
A total of 171 of 670 patients who received sunitinib or sorafenib had cardiovascular events. The incidence rates for CHF/CM, AMI, and stroke were 0.87, 0.14, and 0.14 per 1000 person-days, respectively. Sunitinib or sorafenib use was associated with an increased risk of cardiovascular events (HR, 1.38; 95% confidence interval [CI], 1.02-1.87) and especially stroke (HR, 2.84; 95% CI, 1.52-5.31) in comparison with 788 patients diagnosed with advanced RCC from 2007 to 2009 who were eligible for Part D but did not receive either agent. In subgroup analyses, patients who were 66 to 74 years old at diagnosis had the highest increased risk of stroke associated with the use of either or both drugs.
Sunitinib and sorafenib might be associated with an increased risk of cardiovascular events and particularly stroke.
索拉非尼和舒尼替尼均为口服血管内皮生长因子受体（VEGFR）酪氨酸激酶抑制剂（TKIs），分别于2005年和2006年被批准用于治疗肾细胞癌（RCC）患者。开展了一项基于人群的观察性队列研究，以评估老年RCC患者接受VEGFR TKI治疗的心血管风险。
本研究利用监测、流行病学与最终结果-医疗保险数据库，分析了2000年至2009年间年龄在66岁及以上且被诊断为RCC的患者。通过2010年12月，对包括充血性心力衰竭和心肌病（CHF/CM）、急性心肌梗死（AMI）、中风及心血管死亡在内的心血管不良事件发生率进行了检查。构建Cox比例风险模型以计算风险比（HR），并对年龄、性别、合并症及其他全身治疗的使用情况进行了校正。
在670例接受舒尼替尼或索拉非尼治疗的患者中，共有171例发生心血管事件。CHF/CM、AMI和中风的发生率分别为每1000人日0.87、0.14和0.14。与2007年至2009年间符合D部分条件但未接受任何一种药物治疗的788例晚期RCC诊断患者相比，使用舒尼替尼或索拉非尼与心血管事件风险增加相关（HR，1.38；95%置信区间[CI]，1.02 - 1.87），尤其是中风（HR，2.84；95%CI，1.52 - 5.31）。在亚组分析中，诊断时年龄在66至74岁的患者使用一种或两种药物与中风风险增加最高相关。
舒尼替尼和索拉非尼可能与心血管事件风险增加相关，尤其是中风。
