First-Line Osimertinib in Patients with Treatment-Naive Somatic or Germline EGFR T790M-Mutant Metastatic NSCLC.

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Abstract In rare cases, patients present with baseline (somatic or germline) Epidermal Growth Factor Receptor (EGFR) Thr790Met (T790M) mutations prior to EGFR tyrosine kinase inhibitor (TKI) treatment. This mutation confers resistance to first and second generation TKIs. Osimertinib is a third generation TKI that is FDA approved for use in patients with the EGFR T790M mutation and who have progressed on TKI treatment. To date, the only presented but unpublished experience with first-line osimertinib treatment in 5 patients with baseline T790M mutations who received osimertinib on an expansion cohort of the phase 1 AURA trial. The proper management of these patients is unclear. The EGFR T790M mutation and concurrent EGFR TKI sensitizing mutations were detected using next generation sequencing of tumor samples as part of standard of care testing. Response to treatment with osimertinib was monitored with CT imaging. When germline mutation evaluation was undertaken, peripheral blood mononuclear cells were sequenced for EGFR mutations. Three patients with recently diagnosed treatment naive metastatic lung adenocarcinoma and either somatic or germline EGFR T790M mutations were treated with osimertinib. All three patients had reduction in tumor burden on CT scan with treatment. This report is the first published description of osimertinib treatment in the first-line metastatic setting for patients with somatic or germline EGFR T790M mutations. Patients had good response, with improvement in symptoms and decreased tumor burden on CT scans. This study suggests osimertinib treatment should be considered for patients with baseline EGFR T790 mutations in the first-line setting.