Salvage Chemotherapy After Pembrolizumab for Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma

Background/Aim: Pembrolizumab-based therapy is widely used for recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC). However, clinical outcomes after subsequent salvage chemotherapy (SCT) remain insufficiently defined. This study evaluated the efficacy of SCT after pembrolizumab in patients with R/M HNSCC. Patients and Methods: This multicenter retrospective study included 36 evaluable patients with R/M HNSCC who received SCT after pembrolizumab between December 2019 and February 2022. The primary endpoint was the objective response rate. Secondary endpoints included the disease control rate, progression-free survival, overall survival, and exploratory clinical factors associated with treatment outcomes. Results: The best overall response to SCT was a complete response in 2 patients, partial response in 8, stable disease in 12, and progressive disease in 14. The overall response rate was 27.8%, and the disease control rate was 61.1%. Median progression-free and overall survival were 4.6 months and 11.5 months, respectively. The overall response rate was significantly higher (>4-fold) in patients with prior surgery and in platinum-naive patients. A combined positive score of 20 or higher for tumor programmed cell death-ligand 1, initial M1 status, and prior surgery were associated with longer progression-free survival in exploratory analyses. Conclusion: SCT after pembrolizumab showed clinically meaningful activity in selected patients with R/M HNSCC. These findings support SCT as a reasonable post-pembrolizumab option, although prospective validation is warranted.