Five-Year Outcomes With Pembrolizumab Versus Chemotherapy as First-Line Therapy in Patients With Non–Small-Cell Lung Cancer and Programmed Death Ligand-1 Tumor Proportion Score ≥ 1% in the KEYNOTE-042 Study
Mené sur 1 274 patients atteints d'un cancer du poumon non à petites cellules de stade localement avancé ou métastatique et présentant un score d'expression tumorale de PD-L1 supérieur ou égal à 1 % (durée médiane de suivi : 61,1 mois), cet essai de phase III compare l'efficacité, du point de vue de la survie globale à 5 ans, et la toxicité du pembrolizumab et d'une chimiothérapie de première ligne
We report 5-year results from the phase III KEYNOTE-042 study (ClinicalTrials.gov identifier: NCT02220894). Eligible patients with locally advanced/metastatic non–small-cell lung cancer (NSCLC) without EGFR/ALK alterations and with programmed death ligand-1 (PD-L1) tumor proportion score (TPS)
≥
1% received pembrolizumab 200 mg once every 3 weeks for 35 cycles or chemotherapy (carboplatin + paclitaxel or pemetrexed) for 4-6 cycles with optional maintenance pemetrexed. Primary end points were overall survival (OS) in PD-L1 TPS
≥
50%,
≥
20%, and
≥
1% groups. Patients who completed 35 cycles of pembrolizumab with
≥
stable disease could begin second-course pembrolizumab upon progression. One thousand two hundred seventy‐four patients were randomly assigned (pembrolizumab, n = 637; chemotherapy, n = 637). Median follow-up time was 61.1 (range, 50.0-76.3) months. OS outcomes favored pembrolizumab (v chemotherapy) regardless of PD-L1 TPS (hazard ratio [95% CI] for TPS
≥
50%, 0.68 [0.57 to 0.81]; TPS
≥
20%, 0.75 [0.64 to 0.87]; TPS
≥
1%, 0.79 [0.70 to 0.89]), with estimated 5-year OS rates with pembrolizumab of 21.9%, 19.4%, and 16.6%, respectively. No new toxicities were identified. Objective response rate was 84.3% among 102 patients who completed 35 cycles of pembrolizumab and 15.2% among 33 patients who received second-course pembrolizumab. First-line pembrolizumab monotherapy continued to show durable clinical benefit versus chemotherapy after 5 years of follow-up in PD-L1–positive, locally advanced/metastatic NSCLC without EGFR/ALK alterations and remains a standard of care.