A Prospective Observational Study Comparing Chemotherapy Plus Pembrolizumab Versus Nivolumab Plus Ipilimumab With Chemotherapy in Patients With Metastatic Non-Small Cell Lung Cancer and PD-L1 Expression Below 50%

This is a prospective, observational cohort study conducted in patients with metastatic non-small cell lung cancer (NSCLC) and programmed death-ligand 1 (PD-L1) expression below 50% who are treated in routine clinical practice.

Eligible patients will receive systemic treatment according to standard-of-care decisions made by their treating physicians. Two commonly used treatment approaches will be observed: chemotherapy combined with pembrolizumab, and nivolumab plus ipilimumab administered in combination with chemotherapy. No randomization, protocol-driven treatment assignment, or experimental intervention will be performed as part of the study.

The primary objectives of the study are to compare progression-free survival (PFS) and overall survival (OS) between the two treatment approaches. Survival outcomes will be assessed using standard clinical and radiological follow-up data collected during routine care.

Secondary objectives include the evaluation of health-related quality of life and patient-reported outcomes. Quality of life will be assessed using validated questionnaires administered during routine follow-up visits, including global quality of life, functional status, cognitive function, and psychological well-being.

In addition to the primary and secondary objectives, exploratory analyses are planned to investigate the association between treatment outcomes and selected patient-related factors. These include biological age metrics, exposure to antibiotics during treatment, and dietary patterns assessed through patient questionnaires. These analyses will be conducted in subsets of patients with available and complete data for the relevant variables.