The University of Texas MD Anderson Cancer Center, Houston, TX, United States.
Bern University Hospital, Bern, Switzerland.
Eur J Cancer. 2014 Aug;50(12):2162-70. doi: 10.1016/j.ejca.2014.05.013. Epub 2014 Jun 12.
To define cardiovascular (CV) risk and reversibility of cardiac events in patients who received sunitinib versus comparator treatment (interferon-alfa or placebo).
We performed a retrospective adjudication of comprehensive CV adverse events (AEs) from two phase 3 trials. Components of the comprehensive CV AE end-point comprised hypertension, symptomatic and asymptomatic left ventricular ejection fraction decreases (SD-LVEF; AD-LVEF) and extent of reversibility, heart-failure symptoms, thromboembolic events, dysrhythmia and CV death. Three cardiologists and one oncologist, blinded to treatment allocation, adjudicated suspected CV AEs in the pooled trial database (N=1090).
Incidence rates (IR) for sunitinib versus Interferon-alfa (IFN-α)/placebo were hypertension: 6.9 versus 2.6 (hazard ratio (HR), 3.1; 95% confidence interval (CI), 2.4-4.0); SD-LVEF: 0.4 versus 0.2 (HR, 2.5; 95% CI, 1.0-6.2); AD-LVEF: 1.1 versus 0.8 (HR, 2.1; 95% CI, 1.3-3.4); and composite CV AE end-point: 10.1 versus 4.8 (HR, 2.5; 95% CI, 2.0-3.1), however reversibility, not previously quantified, was found to be clinically meaningful.
Hypertension and SD-LVEF/AD-LVEF were significantly higher with sunitinib versus IFN-α/placebo. Among patients who experienced a cardiac event, symptomatic and asymptomatic instances of decreased cardiac dysfunction were adjudicated as reversible in 47 of 83 (56%) and 17 of 30 (57%), respectively. Among sunitinib-treated patients, many were able to resume sunitinib dosing following resolution of events, a finding that is important for clinical care. In comparator groups, symptomatic and asymptomatic instances were adjudicated as reversible in 4 of 6 (66.7%) and 11 of 21 (52%), respectively. Thromboembolic, dysrhythmic and/or CV deaths were not significantly higher in sunitinib-treated patients.
定义接受舒尼替尼治疗与对照治疗（干扰素-α或安慰剂）的患者的心血管（CV）风险和心脏事件的逆转。
我们对两项 3 期试验的全面 CV 不良事件（AE）进行了回顾性裁决。综合 CV AE 终点的组成部分包括高血压、有症状和无症状左心室射血分数降低（SD-LVEF；AD-LVEF）和逆转程度、心力衰竭症状、血栓栓塞事件、心律失常和 CV 死亡。三位心脏病专家和一位肿瘤学家，对联合试验数据库（N=1090）中可疑 CV AE 进行了盲法治疗分配。
舒尼替尼与干扰素-α（IFN-α）/安慰剂相比的发生率（IR）为高血压：6.9 比 2.6（风险比（HR），3.1；95%置信区间（CI），2.4-4.0）；SD-LVEF：0.4 比 0.2（HR，2.5；95% CI，1.0-6.2）；AD-LVEF：1.1 比 0.8（HR，2.1；95% CI，1.3-3.4）；综合 CV AE 终点：10.1 比 4.8（HR，2.5；95% CI，2.0-3.1），但可逆转性，以前未量化，被认为具有临床意义。
与 IFN-α/安慰剂相比，舒尼替尼治疗的高血压和 SD-LVEF/AD-LVEF 显著更高。在发生心脏事件的患者中，47 例（56%）和 17 例（57%）有症状和无症状的心脏功能障碍降低被裁决为可逆转。在舒尼替尼治疗的患者中，许多患者在事件缓解后能够恢复舒尼替尼治疗，这一发现对临床护理很重要。在对照组中，有症状和无症状的病例分别被裁决为 4 例（66.7%）和 11 例（52%）可逆转。舒尼替尼治疗的患者中血栓栓塞、心律失常和/或 CV 死亡的发生率没有显著升高。
