Clinical and molecular features of epidermal growth factor receptor (Egfr) mutation positive non‐small‐cell lung cancer (nsclc) patients treated with tyrosine kinase inhibitors (tkis): Predictive and prognostic role of co‐mutations

Background: Tyrosine kinase inhibitors (TKIs) show variable efficacy in epidermal growth factor receptor mutation‐positive (EGFR+) NSCLC patients, even in patients harbouring the same mutation. Co‐alterations may predict different outcomes to TKIs. Methods: We retrospectively analysed all consecutive EGFR+ advanced NSCLC treated with first‐line TKIs at our Institutions. NGS with a 22 genes clinical panel was performed on diagnostic specimens. PD‐L1 expression was also evaluated. Results: Of the 106 analysed specimens, 59 showed concomitant pathogenic mutations. No differences in OS (mOS 22.8 vs. 29.5 months; p = 0.088), PFS (mPFS 10.9 vs. 11.2 months; p = 0.415) and ORR (55.9% vs. 68.1%; p = 0.202) were observed comparing patients without and with co‐alterations. Subgroup analysis by EGFR mutation type and TKIs generation (1st/2nd vs. 3rd) did not show any difference too. No correlations of PD‐L1 expression levels by co-mutational status were found. Significant associations with presence of co‐alterations and younger age (p = 0.018) and baseline lymph nodes metastases (p = 0.032) were observed. Patients without concomitant alterations had a significant higher risk of bone progression (26.5% vs. 3.3%, p = 0.011). Conclusions: Pathogenic co‐alterations does not seem to predict survival nor efficacy of EGFR TKIs in previously untreated advanced NSCLC.