PD-1/PD-L1 Checkpoint Immunotherapy vs. Standard Chemotherapy in Advanced Non-Small Cell Lung Cancer

Non-small cell lung cancer (NSCLC) accounts for approximately 85 percent of all lung cancer diagnoses globally and remains the leading cause of cancer-related mortality, with five-year survival rates below 20 percent for patients presenting with metastatic disease at diagnosis. The development of immune checkpoint inhibitors targeting the PD-1/PD-L1 axis has fundamentally transformed first-line treatment paradigms for advanced NSCLC over the past decade, demonstrating superior progression-free and overall survival compared to platinum-based chemotherapy in patients with PD-L1 expression above 50 percent. However, the optimal biomarker strategy for patient selection, the management of immune-related adverse events (irAEs), and the comparative efficacy across PD-L1 expression subgroups remain incompletely characterised in European population cohorts.This phase III randomised controlled trial enrolled 624 patients with treatment-naive advanced NSCLC (stage IIIB/IV) across eight oncology centres in Sweden, Italy, Turkey, and Germany. Patients were randomised 1:1 to pembrolizumab plus chemotherapy versus chemotherapy alone, stratified by PD-L1 expression, histological subtype, and ECOG performance status. Primary endpoints were progression-free survival (PFS) and overall survival (OS); secondary endpoints included objective response rate (ORR), irAE profile, tumour mutational burden (TMB) correlation, and quality of life. The immunotherapy arm demonstrated a median PFS of 18.4 months versus 8.2 months in the chemotherapy arm (HR=0.52, 95% CI 0.41–0.66, p<0.001), with PD-L1 ≥50% patients showing an ORR of 64.6 percent.