EGFR E746_S752delinsV

In summary, there are limited prospective data to guide therapy in patients with rare EGFR mutations. Prospective studies are required to evaluate the response to endothelial growth factor receptor-tyrosine kinase inhibitors in patients with rare EGFR mutations in order to ensure patient safety and response to treatment in this patient population.

In advanced NSCLC patients with EGFR Ex19del, the efficacy of first-line TKIs therapy was affected by the presence of pleural metastasis, Ex19del subtypes and different generation of TKIs.

The EGFR exon 19 deletion-insertion mutations exhibited limited sensitivity to 3rd generation TKI. Moreover, in light of therapeutic effect for the subtype, L747_T751delinsP achieved longer PFS.

This retrospective cohort study furnish the evidence that therapeutic responses and survival of untreated NSCLC population with EGFR 19delins mutation are equal to those with common EGFR 19del mutation after administration of EGFR TKIs therapy.

In the subset who had progressed on osimertinib, afatinib also yielded a superior progression-free survival (6.2 mo) than non-afatinib therapies (1.0 mo, HR = 0.04, p = 0.005) and alternative EGFR TKIs (1.8 mo, HR = 0.06, p = 0.033). EGFR G724S emerges as a resistant mutation against EGFR TKI preferentially in the context of a rare variant of 19del, whereas it might mediate differential mechanisms in the context of exon 20 mutation. We also found that afatinib could be a potential therapeutic option for patients with NSCLC with G724S.

EGFR exon 19 starting at codon 729 to 761, our data showed the deletions occur throughout almost the entire exon 19 amino acid . As our integrated data results, EGFR exon 19 has many different deletions and insertion subtypes could be defined as 79 subtypes . Among those subtypes,70 were complex with an accompanying insertion .

Results EGFR G724S was identified from 2 patients prior to the administration of any treatment, (baseline) from 1 patient after gefitinib failure and from 5 patients after osimertinib failure. Conclusion Our study provides clinical evidence that afatinib monotherapy could be a potential therapeutic option for NSCLC patients with EGFR G724S. Further studies for evaluating the efficacy of afatinib in advanced NSCLC patients harboring EGFR G724S and the underlying resistance mechanism are warranted.