Inframe base pair insertions in exon 20 also result in constitutive activation of EGFR, but unlike the classical activating EGFR mutations, EGFR exon 20 insertions are associated with de novo resistance to current clinically available EGFR inhibitors.19,20 Low response rates of between 3–8% for erlotinib, gefitinib and the second generation EGFR inhibitor afatinib have been reported in EGFR exon 20 insertion mutant NSCLC patients (Table 1),21,22 and thus, effective treatment options are limited. This evidence concerns the gene EGFR and non-small cell lung carcinoma.