First-Line Pembrolizumab With or Without Chemotherapy for Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma
According to long-term follow up results from the phase 3 KEYNOTE-048 study, first-line pembrolizumab with or without chemotherapy continued to prolong survival compared to cetuximab plus chemotherapy among patients with recurrent or metastatic head and neck squamous cell carcinoma.
In this study, 882 previously untreated patients were randomized on a 1-to-1-to-1 basis to receive pembrolizumab with or without chemotherapy, or cetuximab plus chemotherapy. Primary end points included overall survival (OS) and progression-free survival (PFS).
Pembrolizumab monotherapy prolonged OS among patients with a PD-L1 combined positive score (CPS) of ≥ 20 (hazard ratio [HR] 0.61; 95% confidence interval [CI], 0.69 to 0.97), among patients with a PD-L1 CPS ≥ 1 (HR 0.74; 95% CI, 0.61 to 0.89), and in the intention-to-treat population (HR 0.82; 95% CI, 0.69 to 0.97). Pembrolizumab plus chemotherapy prolonged OS among patients with a PD-L1 CPS ≥ 20 (HR 0.63; 95% CI, 0.47 to 0.84), among patients with a PD-L1 CPS ≥ 1 (HR 0.65; 95% CI, 0.53 to 0.79), and in the intention-to-treat population (HR 0.72; 95% CI, 0.60 to 0.86). In the intention-to-treat population, the 5-year OS rate was 14.4% in the pembrolizumab monotherapy arm compared to 6.5% in the cetuximab plus chemotherapy arm. The 5-year OS rate was 16% in the pembrolizumab plus chemotherapy arm compared to 5.2% in the cetuximab plus chemotherapy arm. Across all populations, no clinically meaningful difference in PFS between the arms was observed.
“These 5-year follow-up results support the use of pembrolizumab and pembrolizumab-chemotherapy as first-line standards of care,” concluded Dr Tahara et al.
Source:
Tahara M, Greil R, Rischin D, et al. 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. Eur J Cancer. Published online: April 4, 2025. doi: 10.1016/j.ejca.2025.115395
