EP1.01-68 Impact of EGFR Genotype on the Efficacy of Osimertinib in Patients with Non-Small Cell Lung Cancer: A Prospective Observational Study

Abstract

A T790M of the epidermal growth factor receptor (EGFR) is the most frequently encountered mutation occurring acquired resistance to EGFR tyrosine kinase inhibitors (TKIs) in non-small cell lung cancer (NSCLC). The aim of this study was to assess the differential clinical outcomes of osimertinib therapy in NSCLC patients with T790M according to the type of active EGFR mutation, i.e. exon 19 deletion or L858R point mutation. We conducted a prospective observational cohort study to evaluate the efficacy and safety of osimertinib in patients with major EGFR mutation and T790M-positive advanced NSCLC who had disease progression after first-line EGFR-TKI therapy. The efficacy of osimertinib was evaluated according to the type of EGFR mutation. A total of 51 patients were included in this study. The exon 19 deletion was found in 33 (65%) patients, and the L858R point mutation in 18 patients (35%). An objective response was obtained in 29 patients, indicating an objective response rate of 58.8%. The response rate was 69.7% in patients with exon 19 deletion and 38.9% in patients with L858R point mutation, indicating a statistically significant difference (P =0.033). The median progression-free survival (PFS) and overall survival (OS) of the entire patient population were 7.8 and 15.5 months, respectively. Median PFS in the exon 19 deletion and L858R point mutation groups was 8.0 months and 5.2 months, respectively, indicating a statistically significant difference (P =0.045). Median OS in the exon 19 deletion and L858R point mutation groups was 19.8 months and 12.9 months, respectively, indicating a statistically significant difference (P =0.0015). Multivariate analysis identified exon 19 deletion as a favorable independent predictor of PFS and OS. Investigators should consider the proportions of sensitive EGFR mutation types as a stratification factor in designing or reviewing clinical studies involving osimertinib.