Impact of mutant protein expression on clinical outcomes in patients with EGFR L858R-mutated non-small cell lung cancer.

Background: Currently, patients with epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) are typically treated with osimertinib monotherapy. However, in some patients, the therapeutic efficacy of osimertinib is suboptimal, leading to heterogeneity in treatment response, which presents a clinical challenge. It remains unclear how the expression level of EGFR-mutant protein affects osimertinib treatment and clinical outcomes. In this study, we aimed to examine the association between the expression level of EGFR L858R-mutant protein (EGFR^L858R) and the efficacy of osimertinib by performing immunohistochemical staining of surgical specimens.

Methods: We retrospectively assessed consecutive patients with postoperative recurrent EGFR L858R-mutated NSCLC who received osimertinib monotherapy at five hospitals in Japan between September 2018 and February 2022.

Results: In total, we analyzed 23 patients with postoperative recurrent EGFR L858R-mutated NSCLC. There were no significant differences in objective response rate, progression-free survival, or overall survival for osimertinib monotherapy between the high and low EGFR^L858R-expressing groups. In contrast, high EGFR^L858R expression was associated with shorter disease-free survival (DFS) than low EGFR^L858R expression (log-rank test P=0.008). Furthermore, EGFR^L858R expression was positively correlated with the percentage of Ki-67-positive cells in tumors (P=0.03).

Conclusions: According to our limited data (n=23), the expression level of EGFR^L858R affected only the DFS, with no significant effects on other aspects of survival or treatment efficacy.