Pembrolizumab versus Chemotherapy for PD-L1–Positive NSCLC (KEYNOTE-024)

Pembrolizumab (anti-PD-1) had shown activity in NSCLC. KEYNOTE-024 tested it as first-line therapy in patients with high PD-L1 expression (TPS ≥50%) and no targetable mutations.

Multicenter RCT (n=305) comparing pembrolizumab vs. platinum-based chemotherapy as first-line treatment in advanced NSCLC with PD-L1 TPS ≥50%.

Pembrolizumab significantly improved PFS (10.3 vs 6.0 months, HR 0.50, p<0.001) and OS (30.0 vs 14.2 months, HR 0.63). Response rate was higher (44.8% vs 27.8%). Fewer grade 3–5 adverse events with pembrolizumab.

Pembrolizumab monotherapy is first-line standard of care for advanced NSCLC with PD-L1 TPS ≥50% and no EGFR/ALK mutations. PD-L1 testing is mandatory before first-line therapy. This trial established immunotherapy as first-line treatment for NSCLC.

Excluded EGFR/ALK-positive patients. PD-L1 TPS ≥50% is a high threshold — most patients have lower expression.