PD-L1 Expression as a Predictor of Time to Progression in Metastatic Non-Small Cell Lung Cancer Treated with Immune Checkpoint Inhibitors: A Retrospective Single-Center Study

Background/Objectives: Programmed death-ligand 1 (PD-L1) expression is commonly used as a predictive biomarker in metastatic non-small cell lung cancer (NSCLC); however, its clinical utility in real-world settings remains uncertain. This study evaluated the association between PD-L1 expression and treatment outcomes in patients receiving immune checkpoint inhibitors (ICIs). Methods: In this retrospective, single-center study, 86 patients with metastatic NSCLC treated with ICIs (pembrolizumab or atezolizumab) between January 2020 and December 2025 were included. PD-L1 expression was assessed using 22C3 or SP263 assays and categorized as <50% and ≥50%. The primary endpoint was time to progression (TTP), while the secondary endpoint was objective response rate (ORR). Survival analyses were performed using Kaplan–Meier estimates, log-rank tests, and Cox proportional hazards models. Results: PD-L1 data were available for 78 of the 86 patients. The median age was 66 years (IQR 61–73); 76.7% of patients were male and 65.1% were former smokers. Adenocarcinoma was the predominant histological subtype (47.7%), followed by squamous cell carcinoma (41.9%). The ORR was similar between treatment groups (atezolizumab: 62.5%; pembrolizumab: 64.9%; p = 0.84). No statistically significant difference in TTP was observed between PD-L1 <50% and ≥50% groups. Kaplan–Meier analysis showed no statistically significant difference in TTP between PD-L1 groups (log-rank p = 0.094), although a numerical trend toward shorter TTP was observed in patients with PD-L1 ≥50%. In multivariate Cox regression analysis, PD-L1 ≥50% was not associated with TTP (hazard ratio [HR] 1.53, 95% confidence interval [CI] 0.77–3.05; p = 0.20). No other clinical variables, including smoking status and liver metastases, were significantly associated with outcomes. Conclusions: In this limited, retrospective single-center cohort with a heterogeneous treatment mix (chemo-immunotherapy and immunotherapy monotherapy), PD-L1 expression was not significantly associated with treatment response or time to progression. While these results should be interpreted cautiously given the modest sample size and the small number of progression events, they are consistent with broader real-world evidence indicating that PD-L1 expression alone may not reliably stratify clinical benefit in metastatic NSCLC. Larger prospective studies integrating PD-L1 with complementary biomarkers are needed to confirm these observations.