Osimertinib for Uncommon Endothelial Growth Factor Receptor-Mutant Non-Small Cell Lung Carcinoma: A Case Report

Non-small cell lung cancer (NSCLC) accounts for 84% of all lung cancers and continues to remain the leading cause of cancer-related mortality worldwide. The advent of gene targeted therapies has changed the landscape of NSCLC management. Osimertinib is a third-generation tyrosine kinase inhibitor (TKI) that has activity against exon 19, exon 21 (L858R) mutations. It is also active against T790M mutation which is the most common resistant mechanism to earlier generation TKIs. Activity of osimertinib against rare EGFR mutations is largely unknown. We report the case of a 64-year-old woman with metastatic NSCLC carrying an exceedingly rare deletion-insertion exon 19 EGFR mutation (p.E746_S752delinsV) who demonstrated sustained disease control with osimertinib, achieving a progression-free survival of 26 months.

A 64-year-old nonsmoker female presented with back pain for 1 month. Magnetic resonance imaging spine showed pathological fracture secondary to multiple lytic lesions. She underwent FDG PET/CT that showed large left lower lobe mass, bilateral pulmonary nodules, widespread osteolytic lesions. She underwent iliac lytic lesion biopsy that was consistent with adenocarcinoma (TTF1- and CK7-positive). Tumor tissue next-generation sequencing showed EGFR exon 19 mutation (DNA change: c.2237_2255delinsT, amino acid change: p.E746_S752delinsV [Glu 746_Ser752delinsval]). She was started on osimertinib and showed clinical response within 2 weeks of starting therapy. She was able to maintain a response for 26 months since starting treatment.

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.