Abstract
Abstract Targeted inhibition of epidermal growth factor receptor (EGFR) signaling has emerged as the standard of care for EGFR mutation-positive non-small cell lung cancer (EGFRm+ NSCLC). Afatinib, an oral irreversible ErbB-family blocker, has been extensively studied in this context. Recent studies have highlighted the benefit and tolerability of afatinib treatment in patients with EGFRm+ advanced/metastatic NSCLC. The LUX-Lung 3 and 6 phase III studies showed greater efficacy with first-line afatinib compared with platinum-doublet chemotherapy, whereas LUX-Lung 7 highlighted the enhanced benefits of afatinib over the first-generation EGFR tyrosine kinase inhibitor (TKI), gefitinib. The nearly inevitable emergence of resistance to afatinib, coupled with recent data for the third-generation TKI osimertinib, highlight the need to identify an optimal treatment sequencing strategy to achieve long-term benefit and survival. The available data suggest that optimal treatment could involve first-line afatinib, followed by osimertinib upon acquired resistance to afatinib through the T790M mutation. This review discusses the pharmacology of afatinib, efficacy and safety results of key trials in the afatinib clinical study program, management of adverse events, and sequencing strategies following acquired resistance. Afatinib data are discussed in the context of recent studies of other EGFR TKIs, to provide considerations around their use and inform potential sequential treatment approaches.
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