Real-World Comparison of PD-1 and PD-L1 Inhibitor Monotherapy in Metastatic Non-Small Cell Lung Cancer with High PD-L1 Expression

Background: Immune checkpoint inhibitor monotherapy targeting the PD-1/PD-L1 axis is a standard first-line treatment option for patients with metastatic non-small cell lung cancer (NSCLC) and high PD-L1 expression. However, comparative real-world data evaluating PD-1 versus PD-L1 inhibitor monotherapy in this population remain limited. Methods: We conducted a retrospective, single-center real-world analysis of patients with metastatic NSCLC and high PD-L1 expression who initiated first-line immune checkpoint inhibitor monotherapy between May 2024 and January 2025. Patients were treated with either pembrolizumab (PD-1 inhibitor) or atezolizumab (PD-L1 inhibitor) as monotherapy. Progression-free survival (PFS) was estimated using the Kaplan–Meier method and compared using the log-rank test. Univariable and multivariable Cox proportional hazards regression models were applied to identify clinical factors associated with PFS. Results: A total of 125 patients were included, of whom 73 received pembrolizumab and 52 received atezolizumab. The median PFS was numerically longer in patients treated with pembrolizumab compared with atezolizumab (9.93 vs. 5.33 months), although this difference did not reach statistical significance (HR 1.14, 95% CI 0.74–1.74; p = 0.559). Poor performance status (ECOG PS 2) was independently associated with inferior PFS (HR 3.22, 95% CI 2.02–5.12), whereas very high PD-L1 expression (TPS 90–100%) was independently associated with improved PFS (HR 0.57, 95% CI 0.35–0.93). Conclusions: In this real-world cohort, pembrolizumab was associated with numerically longer PFS than atezolizumab; however, this difference was not statistically significant. Outcomes were primarily driven by baseline clinical factors, particularly performance status and the degree of PD-L1 expression. Larger cohorts with longer follow-up are warranted to clarify potential differences and assess long-term outcomes.