First-(gefitinib, erlotinib) and second-(afatinib, dacomitinib) generation EGFR TKIs have been considered the standard first-line therapy for many years for EGFR mutant NSCLC but, even though the responses are generally solid and sustained, the onset of acquired resistance is universal and occurs mostly through on-target mechanisms (EGFR-dependent mechanisms) after a median of 9 to 12 months of treatment [9–11]. The gene discussed is EGFR; the disease is non-small cell lung carcinoma.