Mutations in the epidermal growth factor receptor (EGFR) gene are present in more than 15–20% of patients with non-small cell lung cancer (NSCLC). These are mostly classical activating mutations – deletions in exon 19 and L858R point mutations in exon 21. Both mutations are sensitive to EGFR tyrosine kinase inhibitors (TKIs), which have become the accepted standard of first-line treatment for advanced EGFR-mutated NSCLC. However, 10 to 20% of EGFR-positive NSCLC cases have less common mutations, including exon 20 mutations, for which the response to EGFR TKI therapy can vary significantly depending on the type of mutation, and the choice of optimal therapy remains a challenge. Here, we present a description of a clinical case of successful and durable response to first-generation (within a year) and then third-generation (more than 7 years) TKI therapy in metastatic NSCLC with a rare EGFR exon 20 mutation. Treatment is still ongoing.

Keywords: osimertinib, exon 20, rare mutation, EGFR, non-small cell lung cancer