Real-world comparison of pembrolizumab alone and combined with chemotherapy in metastatic lung adenocarcinoma patients with PD-L1 expression ≥50

H H Hektoen; K M Tsuruda; O T Brustugun; K Neumann; B K Andreassen

doi:10.1016/j.esmoop.2025.105073

Real-world comparison of pembrolizumab alone and combined with chemotherapy in metastatic lung adenocarcinoma patients with PD-L1 expression ≥50

ESMO Open. 2025 Apr 29;10(5):105073. doi: 10.1016/j.esmoop.2025.105073. Online ahead of print.

Authors

H H Hektoen¹, K M Tsuruda², O T Brustugun³, K Neumann⁴, B K Andreassen⁵

Affiliations

¹ Department of Research, Cancer Registry of Norway, Norwegian Institute of Public Health Oslo, Norway; Department of Cancer Genetics, Institute for Cancer Research, Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway. Electronic address: https://twitter.com/HektoenHH.
² Department of Research, Cancer Registry of Norway, Norwegian Institute of Public Health Oslo, Norway.
³ Section of Oncology, Drammen Hospital, Vestre Viken Health Trust, Drammen, Norway; Institute for Clinical Medicine, Faculty of Medicine, University of Oslo, Norway.
⁴ Department of Pulmonology, Akershus University Hospital, Lørenskog, Norway.
⁵ Department of Research, Cancer Registry of Norway, Norwegian Institute of Public Health Oslo, Norway. Electronic address: b.k.andreassen@kreftregisteret.no.

PMID: 40305908
DOI: 10.1016/j.esmoop.2025.105073

Abstract

Objectives: The frontline treatment of metastatic lung adenocarcinoma with high Programmed death-ligand 1 (PD-L1) expression (≥50%) includes immune checkpoint inhibitors (ICIs) either as monotherapy or combined with chemotherapy. The added benefit of chemotherapy in this context lacks direct comparison in head-to-head trials. We aimed to compare these two ICI treatment modalities both overall and within relevant patient subgroups in a real-world setting.

Materials and methods: This retrospective, nationwide study included 410 individuals diagnosed in Norway during 2017 to 2021 with stage IV non-small-cell lung adenocarcinoma, PD-L1 expression ≥50%, and treated first line with the ICI pembrolizumab, either as monotherapy (n = 317) or in combination with platinum-based chemotherapy (n = 93). We analyzed early (6-month) and overall (3-year) risk of death after treatment initiation using Cox regression, adjusted for and stratified by sex, age, stage, PD-L1 expression, performance status, and education.

Results: Patients treated with combination therapy had a higher median overall survival compared with monotherapy (22.6 months versus 14.2 months), and reduced risk of overall death, although not statistically significant after adjustment [hazard ratio (HR) 0.74, 95% confidence interval (CI) 0.54-1.00]. However, the risk of early death was significantly lower in patients receiving combination therapy, even after adjustment (HR 0.41, 95% CI 0.23-0.76). Across most subgroups, patients receiving combination therapy had comparable or superior survival outcomes relative to those receiving monotherapy. Particularly noteworthy were the observed benefits from combination therapy over monotherapy among females, individuals with stage IVB disease, and those with PD-L1 expression exceeding 75%.

Conclusion: Our real-world study demonstrates that combination therapy with ICI and chemotherapy provides superior early survival benefits over monotherapy in PD-L1-high patients. Additionally, certain subgroups showed enhanced overall survival. These findings challenge current treatment practices and underscore the need for further validation to optimize patient selection for monotherapy versus combination therapy, in particular to reassess the role of PD-L1 in treatment decisions.

Keywords: chemotherapy; immune checkpoint inhibitors; immunotherapy; non-small-cell lung cancer; overall survival; pembrolizumab.