Michael S Ewer1, Kalpesh Patel2, Dennis O'Brien2, Robert M Lorence2. 1. Department of Cardiology, Division of Medical Specialties, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX, 77030, USA. mewer@mdanderson.org. 2. Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT, USA.
Abstract
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.
BACKGROUND:Afatinib is an oral irreversible ErbB family blocker that targets epidermal growth factor receptor (EGFR/ErbB1), humanepidermal 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 EGFRtyrosine kinase inhibitor-pretreated NSCLCpatients (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.
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