Objective: Differences in efficacy of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKI) have been observed between non-small cell lung cancer (NSCLC) patients with 19 exon deletion (19Del)  and L858R  mutation. We explored whether the total number or pattern of concomitant mutations of 19Del  and L858R  may explain their different sensitivities.
Patients and Methods: This study contained the mutational profiles of EGFR-mutated NSCLC patients from two cohorts: Guangzhou (G1) and database (G2). Concomitant mutation status and EGFR-TKI response information were retrieved.
Results: A total of 403 patients covered 283 genes in the G1 and 803 patients with a different gene set in the G2 were included. Similar prevalence of total concomitant mutation number was observed in both G1 ( 19Del  32.48% vs L858R  30.45%; P =0.68) and G2 ( 19Del  74.9% vs L858R  73.2%; P =0.65) cohorts. Only HGF/c-Met  pathway same more related to L858R  mutation. EGFR-TKI response information was recorded for 134 patients in the G2 cohort. 19Del  showed a higher objective response (OR) rate compared with L858R , regardless of concomitant mutations. Compared to patients with OR, non-OR patients had more concomitant mutations, both in 19Del  (53.8% vs 83.3%; P =0.021) and L858R  (51.4% vs 77.8%; P =0.029). In particular, total concomitant mutations (OR=0.27; P =0.03), sensitive EGFR  mutations (OR=2.21; P =0.04), and T790M  (OR=0.244; P =0.02) significantly affected the TKI response.
Conclusion: Concomitant mutations were widespread in 19Del  and L858R  and were associated with poorer OR to EGFR-TKIs. However, 19Del  and L858R  had similar numbers and patterns of concomitant mutations, which might not explain the different sensitivity to EGFR-TKI.
Keywords: epidermal growth factor receptor mutation, 19Del, L858R, non-small cell lung cancer, concomitant mutation