- Pembrolizumab monotherapy yielded a survival advantage with lower toxicity than standard chemotherapy in patients with previously untreated locally advanced or metastatic NSCLC and a programmed death ligand 1 (PD-L1) tumor proportion score (TPS) ≥1%.
- Pembrolizumab efficacy rose with TPS score.
Why this matters
- This study formed the basis of the FDA's lowering of the TPS cutoff from ≥50% to ≥1% in stage III NSCLC.
- International, randomized, phase 3 KEYNOTE-042 trial.
- 1274 patients with locally advanced or metastatic NSCLC and a PD-L1 TPS of ≥1% received first-line therapy with pembrolizumab monotherapy (n=637) or platinum-based chemotherapy (n=637).
- Funding: MSD.
- Pembrolizumab yielded significantly better OS than chemotherapy (TPS ≥50%: HR, 0.69 [P=.0003]; TPS ≥20%: HR, 0.77 [P=.0020]; and TPS ≥1%: HR, 0.81 [P=.0018]).
- Median OS was longer with pembrolizumab vs chemotherapy (TPS ≥50%: 20 vs 12.2 months; TPS ≥20%: 17.7 vs 13.0 months; TPS ≥1%: 16.7 vs 12.1 months).
- Fewer any-grade treatment-related adverse events (63% vs 90%) and fewer grade ≥3 toxicities (18% vs 41%) with pembrolizumab.
- Open-label design.