Cardiac safety of afatinib: a review of data from clinical trials. Issue 1 (December 2015)

• Record Type: Journal Article
• Authors: Ewer, Michael; Patel, Kalpesh; O'Brien, Dennis; Lorence, Robert
• Is Part Of: Cardio-oncology. Volume 1:Issue 1(2015)
• Page Start: 1
• Page End: 8
• Publication Date: 2015-12
• Subjects: Afatinib -- Cardiac safety -- Non–small cell lung cancer -- Tyrosine kinase inhibitor; Cancer -- Treatment -- Complications -- Periodicals; Cancer -- Chemotherapy -- Complications -- Periodicals; Cardiovascular system -- Periodicals; Cardiovascular pharmacology -- Periodicals; 616.99406
• DOI: 10.1186/s40959-015-0006-7
• Languages: English
• ISSNs: 2057-3804

Abstract

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 sensitizingEGFR 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 withEGFR 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.