Pembrolizumab with or without chemotherapy in HNSCC: PD-L1 CPS-stratified analysis of updated KEYNOTE-048 data

Based on KEYNOTE-048 results, pembrolizumab monotherapy and pembrolizumab plus chemotherapy are established first-line treatments for recurrent or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) with PD-L1 combined positive score (CPS) ≥ 1. Researchers from Jilin University (China) carried out an analysis of updated KEYNOTE-048 data to compare both treatments in CPS 1-9 and CPS ≥ 20 subgroups. Among 499 patients with CPS ≥ 1, 240 (48.1%) had CPS 1-19 and 259 (51.9%) had CPS ≥ 20. In the CPS 1-19 subgroup, pembrolizumab-chemotherapy showed numerically longer progression-free survival on next-line therapy (PFS2; 10.8 versus 8.0 months; HR 0.81; 95% CI 0.62-1.06) and overall survival (OS; 12.8 versus 10.8 months; HR 0.87; 95% CI 0.67-1.15) versus monotherapy, without statistical significance. For CPS ≥ 20 patients, efficacy was comparable between regimens, with similar PFS2 (11.3 versus 11.7 months) and OS (14.7 versus 14.9 months). Restricted mean survival time analyses and landmark analyses showed an early PFS2 benefit and a trend toward OS benefit with pembrolizumab-chemotherapy in CPS 1-19, with comparable outcomes in CPS ≥ 20. The authors conclude that these results support a refined first-line strategy in R/M HNSCC: monotherapy for CPS ≥ 20 to minimize toxicity, and combination therapy for CPS 1-19 to potentially enhance disease control (graphical abstract).