Pembrolizumab with or without chemotherapy in recurrent or metastatic head and neck squamous cell carcinoma: 5-year f...

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. CLINICAL TRIAL INFORMATION: NCT02358031. PRIOR PRESENTATION: Presented at the European Society for Medical Oncology Congress, September 9-13, 2022.