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 and mutation. We explored whether the total number or pattern of concomitant mutations of and 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 ( 32.48% vs 30.45%; =0.68) and G2 ( 74.9% vs 73.2%; =0.65) cohorts. Only pathway same more related to mutation. EGFR-TKI response information was recorded for 134 patients in the G2 cohort. showed a higher objective response (OR) rate compared with , regardless of concomitant mutations. Compared to patients with OR, non-OR patients had more concomitant mutations, both in (53.8% vs 83.3%; =0.021) and (51.4% vs 77.8%; =0.029). In particular, total concomitant mutations (OR=0.27; =0.03), sensitive mutations (OR=2.21; =0.04), and (OR=0.244; =0.02) significantly affected the TKI response.

CONCLUSION

Concomitant mutations were widespread in and and were associated with poorer OR to EGFR-TKIs. However, and had similar numbers and patterns of concomitant mutations, which might not explain the different sensitivity to EGFR-TKI.