Association Between PD-L1 Expression and Interstitial Lung Disease Risk in EGFR-mutant NSCLC Treated With EGFR-TKIs

Background/Aim: Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are the standard treatment therapy for non-small cell lung cancer (NSCLC) with EGFR mutations. However, patients harboring the exon 21 L858R point mutation (L858R) typically have poorer treatment outcomes than those with exon 19 deletions. Our previous findings suggest that among patients with L858R-positive NSCLC, those with programmed death-ligand 1 (PD-L1) expression may have an increased risk of developing interstitial lung disease (ILD) during EGFR-TKI therapy, potentially compromising treatment continuity and prognosis. This study investigated the association between PD-L1 expression and ILD occurrence in patients with EGFR-mutant NSCLC receiving EGFR-TKIs. Patients and Methods: We retrospectively analyzed patients with EGFR-mutant NSCLC treated with EGFR-TKIs and compared clinical characteristics between those who developed ILD and those who did not. Survival was defined as the interval from initiation of lung cancer treatment to death or last follow-up. Results: Among 76 patients, 11 (14.5%) developed ILD during treatment. The ILD group had a significantly higher proportion of L858R-positive cases compared with the non-ILD group. Multivariate analysis identified L858R mutation and PD-L1 positivity as independent risk factors for ILD. Overall survival was significantly longer in the non-ILD group than in the ILD group (p=0.001). Conclusion: Among patients with EGFR-mutant NSCLC undergoing EGFR-TKI therapy, the presence of the L858R mutation and PD-L1 expression are associated with an elevated ILD risk. Enhanced monitoring and individualized, risk-adapted management strategies are warranted to optimize outcomes for high-risk patients.