Pembrolizumab with or without chemotherapy in recurrent or metastatic head and neck squamous cell carcinoma: 5-year follow-up from the randomized phase III KEYNOTE-048 study
Mené sur 822 patients atteints d'un carcinome épidermoïde de la tête et du cou récidivant ou de stade métastatique (durée médiane de suivi : 69,2 mois), cet essai de phase III évalue l'efficacité, du point de vue de la survie globale et de la survie sans progression, et la toxicité d'un traitement de première ligne par pembrolizumab avec ou sans chimiothérapie
Background: Pembrolizumab monotherapy and pembrolizumab-chemotherapy demonstrated superior overall survival (OS) versus cetuximab-chemotherapy (EXTREME) in the primary analysis of the phase III KEYNOTE-048 study of recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC) in the first-line setting. We report updated data with 5 years of follow-up.
Methods: Adults with previously untreated R/M HNSCC incurable by local therapy were randomly assigned 1:1:1 to pembrolizumab, pembrolizumab plus chemotherapy, or EXTREME. The primary endpoints were OS and progression-free survival (PFS).
Results: Overall, 882 participants were assigned to pembrolizumab, pembrolizumab-chemotherapy, or EXTREME. Median study follow-up was 69.2 months (pembrolizumab) and 68.6 months (pembrolizumab-chemotherapy). Median OS remained longer for pembrolizumab versus EXTREME in the programmed cell death ligand 1 (PD-L1) combined positive score (CPS) ≥20 (HR, 0.61; 95% CI, 0.46-0.81) and CPS ≥1 populations (HR, 0.74; 95% CI, 0.61-0.89), and similar in the total population (HR, 0.82; 95% CI, 0.69-0.97). Pembrolizumab-chemotherapy prolonged median OS in the PD-L1 CPS ≥20 (HR, 0.63; 95% CI, 0.47-0.84), CPS ≥1 (HR, 0.65; 95% CI, 0.53-0.79), and total (HR, 0.72; 95% CI, 0.60-0.86) populations. The 5-year OS rate in the total population was 14.4% for pembrolizumab versus 6.5% for EXTREME and 16.0% for pembrolizumab-chemotherapy versus 5.2% for EXTREME. There was no clinically meaningful difference in PFS among pembrolizumab, pembrolizumab-chemotherapy, or EXTREME groups in any populations.
Conclusions: These 5-year follow-up results support the use of pembrolizumab and pembrolizumab-chemotherapy as first-line standards of care for R/M HNSCC.
European Journal of Cancer , résumé 2024