Real-World Outcomes of First-Line Pembrolizumab Monotherapy in Metastatic NSCLC with High PD-L1 Expression (TPS ≥ 50%): A Multicenter Study from Serbia

Abstract

Background: Pembrolizumab monotherapy is the standard first-line treatment for metastatic non-small cell lung cancer (NSCLC) patients whose tumors express a PD-L1 tumor proportion score (TPS) of ≥50%. However, real-world data regarding its effectiveness outside of clinical trials, particularly in Eastern European populations, are limited. Methods: We conducted a retrospective, multicenter study including 225 patients with metastatic NSCLC and PD-L1 TPS ≥ 50% who received first-line pembrolizumab monotherapy in Serbia between 2019 and 2022. Patient demographics, clinical characteristics, and treatment outcomes were collected. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan–Meier method, and multivariable Cox proportional hazards regression was performed to identify predictors of outcomes. Results: The median PFS was 9.7 months (95% CI: 7.979–11.421), and the median OS was 17.0 months (95% CI: 12.813–20.187) at a median follow-up of 18.1 months. The overall response rate (ORR) was 36.4%, and the disease control rate (DCR) was 73.4%. Multivariable analysis identified good performance status (ECOG PS 0–1), PD-L1 TPS ≥ 90%, and the occurrence of immune-related adverse events (irAEs) as independent predictors of improved PFS and OS. Conclusions: Our study highlights the efficacy and safety of first-line pembrolizumab monotherapy in a real-world Serbian population with metastatic NSCLC and high PD-L1 expression. Furthermore, it confirms the prognostic value of ECOG PS, high PD-L1 expression, and the development of irAEs in predicting favorable clinical outcomes. © 2025 by the authors.