Clinical implications of PD ‐ L1 expression in oncogene‐driven NSCLC : Differential responses to targeted agents and immune checkpoint inhibitors

PD-L1 is a reliable biomarker for predicting immunotherapy efficacy in NSCLC patients without driver gene mutations. However, its significance in patients with driver gene-positive tumors remains unclear. This study analyzed 273 patients with stage IV non-small cell lung cancer harboring driver gene mutations. All patients had PD-L1 expression levels ≥10%. The effect of PD-L1 expression on progression-free survival (PFS) and overall survival (OS) was assessed. Among the 273 patients with driver gene-positive NSCLC, 127 had a PD-L1 tumor proportion score (TPS) of 10-49%, and 146 had TPS ≥50%. Patients in the TPS 10%-49% group had significantly better median PFS and OS compared to those in the TPS ≥50% group (p = 0.0008 and p = 0.0009, respectively). In the realm of targeted therapy, patients who received first-line tyrosine kinase inhibitors (TKIs) showed superior outcomes in the TPS 10-49% group compared to the TPS ≥50% group in terms of both median PFS (30.8 months vs. 13.9 months, p = .0001) and OS (44.8 months vs. 26.3 months, p = .0006). Regarding immunotherapy, PD-L1 expression level was not significantly associated with treatment efficacy. However, in patients with KRAS mutations, those who received first-line immunotherapy exhibited better median PFS and OS (p <.0001 for both). Notably, among patients with high PD-L1 expression, no statistically significant clinical benefit was observed. In NSCLC patients with driver gene mutations, PD-L1 expression is associated with the efficacy of targeted therapy but is not predictive of response to immunotherapy.