Ewer Michael S, Patel Kalpesh, O'Brien Dennis, Lorence Robert M
Department of Cardiology, Division of Medical Specialties, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX, 77030, USA.
Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT, USA.
Cardiooncology. 2015 Nov 26;1(1):3. doi: 10.1186/s40959-015-0006-7.
Afatinib is an oral irreversible ErbB family blocker that targets epidermal growth factor receptor (EGFR/ErbB1), human epidermal growth factor receptor 2 (HER2/ErbB2), and HER4 (ErbB4) and is approved for the first-line treatment of advanced non-small cell lung cancer (NSCLC) with certain sensitizing EGFR mutations. As anti-HER2 therapies have been associated with cardiac dysfunction, we report cardiac safety data for afatinib.
Cardiac data were analyzed from phase III trials of afatinib 40 mg in treatment-naive patients with EGFR mutation-positive NSCLC (LUX-Lung 3 [LL3]; n = 229 afatinib, n = 111 chemotherapy) and afatinib 50 mg in EGFR tyrosine kinase inhibitor-pretreated NSCLC patients (LUX-Lung 1 [LL1]; n = 390 afatinib, n = 195 placebo). Additional pooled data from 49 trials (n = 3865 afatinib-treated patients) is reported. Cardiac failure adverse events (CF-AEs), including symptomatic cardiac failure and depressed left ventricular ejection fraction (LVEF), were analyzed.
Time at risk-adjusted CF-AE rates (events/100 patient-years) were similar for afatinib versus placebo in LL1 (2.40 vs 2.23) and versus chemotherapy in LL3 (2.28 vs 2.92); the pooled afatinib CF-AE rate (2.88) was consistent with that for both trials. The frequency of clinically significant LVEF reductions was higher for chemotherapy in LL3 (2/15 [13.3 %], afatinib 13/208 [6.3 %]; p = 0.267) and similar to placebo in LL1 (5/122 [4.1 %], afatinib 14/304 [4.6 %]; p = 1.000).
Afatinib was not associated with cardiac failure or LVEF reductions in the afatinib clinical trial program.
阿法替尼是一种口服不可逆的表皮生长因子受体（EGFR）家族阻滞剂，可作用于表皮生长因子受体（EGFR/ErbB1）、人表皮生长因子受体2（HER2/ErbB2）和HER4（ErbB4），已被批准用于一线治疗具有特定敏感EGFR突变的晚期非小细胞肺癌（NSCLC）。由于抗HER2治疗与心脏功能障碍有关，我们报告了阿法替尼的心脏安全性数据。
分析了阿法替尼40mg用于初治EGFR突变阳性NSCLC患者的III期试验（LUX-Lung 3 [LL3]；阿法替尼组n = 229，化疗组n = 111）以及阿法替尼50mg用于EGFR酪氨酸激酶抑制剂预处理的NSCLC患者的III期试验（LUX-Lung 1 [LL1]；阿法替尼组n = 390，安慰剂组n = 195）中的心脏数据。还报告了来自49项试验（n = 3865例接受阿法替尼治疗的患者）的汇总数据。分析了心力衰竭不良事件（CF-AE），包括有症状的心力衰竭和左心室射血分数（LVEF）降低。
在LL1中，阿法替尼与安慰剂相比，风险调整后的CF-AE发生率（事件/100患者年）相似（2.40对2.23）；在LL3中，阿法替尼与化疗相比也相似（2.28对2.92）；阿法替尼汇总的CF-AE发生率（2.88）与两项试验一致。在LL3中，化疗导致具有临床意义的LVEF降低的频率更高（2/15 [13.3%]，阿法替尼组13/208 [6.3%]；p = 0.267），在LL1中与安慰剂相似（5/122 [4.1%]，阿法替尼组14/304 [4.6%]；p = 1.000）。
在阿法替尼临床试验项目中，阿法替尼与心力衰竭或LVEF降低无关。
