EGFR exon 19 deletion switch and development of p.L792Q mutation as a new resistance mechanism to osimertinib: a case report and literature review

Pasquale Pisapia, Danilo Rocco, Francesco Pepe, Caterina De Luca, Ciro Battiloro, Riccardo Smeraglio, Miriam Cieri, Claudio Bellevicine, Giancarlo Troncone, Umberto Malapelle


Epidermal growth factor receptor (EGFR) gene mutations play an important role in the treatment management of non-small cell lung cancer (NSCLC) patients. After a first- or second-generation EGFR tyrosine kinase inhibitor (TKI) therapy, the most common resistance mechanism involves the selection of a resistant clone carrying the exon 20 p.T790M point mutation. However, also for these patients, treated with a third-generation TKI (osimertinib) several mechanisms of acquired resistance are described. Here we report the case of a 68-year-old man with an EGFR exon 19 deletion treated with gefitinib in first line and osimertinib in second line besides on the presence of a p.T790M mutation, who developed an uncommon EGFR exon 20 p.L792Q point mutation at the progression to osimertinib, with the concomitant modification of the original sensitizing EGFR exon 19 deletion and the loss of p.T790M mutation.