Cardiac safety of afatinib: a review of data from clinical trials

摘要

Background 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. Methods 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. Results 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). Conclusion Afatinib was not associated with cardiac failure or LVEF reductions in the afatinib clinical trial program.