# Immunotherapy Versus Chemo-Immunotherapy as First-Line Treatment in Metastatic Non-Small Cell Lung Cancer Patients with PD-L1 TPS ≥ 50%: A Real-World Retrospective Study

## TL;DR

This study compares immunotherapy alone versus combined immunotherapy and chemotherapy for lung cancer patients with high PD-L1 levels, finding that very high PD-L1 scores are linked to better survival.

## Contribution

The study provides real-world evidence on treatment outcomes for metastatic NSCLC patients with PD-L1 TPS ≥ 50%, highlighting the potential of monotherapy in those with TPS ≥ 90%.

## Key findings

- Patients with PD-L1 TPS ≥ 90% had significantly better survival outcomes than those with TPS 50–89%.
- No significant survival differences were found between immunotherapy monotherapy and chemo-immunotherapy in the overall cohort.
- Pembrolizumab monotherapy showed numerically better outcomes in patients with TPS ≥ 90%, though not statistically significant.

## Abstract

Background: Immune checkpoint inhibitors (ICIs) have become the standard first-line treatment for patients with metastatic non-small cell lung cancer (NSCLC) with high programmed death-ligand 1 (PD-L1) expression. However, the optimal selection between immunotherapy monotherapy and chemo-immunotherapy in patients with a PD-L1 tumor proportion score (TPS) ≥ 50% remains uncertain in routine clinical practice. Methods: We retrospectively reviewed patients with metastatic NSCLC and a PD-L1 TPS ≥ 50% who initiated first-line treatment with pembrolizumab monotherapy or pembrolizumab combined with platinum-based chemotherapy at the Istanbul Medipol University Department of Medical Oncology between July 2017 and December 2024. Survival outcomes, including progression-free survival (PFS) and overall survival (OS), were evaluated and compared according to PD-L1 expression levels and treatment strategy. Prognostic factors associated with survival outcomes were also explored. Results: A total of 65 patients were included, of whom 36 received pembrolizumab plus chemotherapy and 29 received pembrolizumab monotherapy. The estimated median PFS and OS for the entire cohort were 24.2 months (95% CI, 6.5–33.0) and 34.6 months (95% CI, 6.5–62.7), respectively. Patients with very high PD-L1 expression (TPS ≥ 90%) experienced significantly longer survival outcomes compared with those with a TPS of 50–89%, and a PD-L1 TPS ≥ 90% remained an independent prognostic factor for OS. When treatment strategies were compared across the entire cohort, no statistically significant differences in PFS or OS were observed between immunotherapy monotherapy and chemo-immunotherapy. Hypertension was identified as an independent negative prognostic factor for PFS. In patients with a PD-L1 TPS ≥ 90%, survival outcomes numerically favored pembrolizumab monotherapy, although this difference did not reach statistical significance. Conclusions: In this real-world cohort of patients with PD-L1 high metastatic NSCLC, PD-L1 expression, particularly very high TPS levels, was strongly associated with survival outcomes. While no survival differences were observed between treatment strategies in the overall population, pembrolizumab monotherapy may represent an appropriate first-line option in selected patients with a PD-L1 TPS ≥ 90%. Larger prospective studies are warranted to refine treatment selection in this setting.