Pembrolizumab With or Without Chemotherapy in Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma: Updated Results of the Phase III KEYNOTE-048 Study

Harrington, KJ; Burtness, B; Greil, R; Soulieres, D; Tahara, M; de Castro Jr, G; Psyrri, A; Brana, I; Baste, N; Neupane, P; Bratland, A; Fuereder, T; Hughes, BGM; Mesia, R; Ngamphaiboon, N; Rordorf, T; Wan Ishak, WZ; Lin, J; Gumuscu, B; Swaby, RF; Rischin, D

Author(s): Harrington, KJ; Burtness, B; Greil, R; Soulieres, D; Tahara, M; de Castro Jr, G; Psyrri, A; Brana, I; Baste, N; Neupane, P; Bratland, A; Fuereder, T; Hughes, BGM; Mesia, R; Ngamphaiboon, N; Rordorf, T; Wan Ishak, WZ; Lin, J; Gumuscu, B; Swaby, RF; Rischin, D;
Details: Publication Year 2023,Volume 41,Issue #4,Page 790-802
Journal Title: Journal of Clinical Oncology
Publication Type: Research article
Abstract: PURPOSE: Pembrolizumab and pembrolizumab-chemotherapy demonstrated efficacy in recurrent/metastatic head and neck squamous cell carcinoma in KEYNOTE-048. Post hoc analysis of long-term efficacy and progression-free survival on next-line therapy (PFS2) is presented. METHODS: Patients were randomly assigned (1:1:1) to pembrolizumab, pembrolizumab-chemotherapy, or cetuximab-chemotherapy. Efficacy was evaluated in programmed death ligand 1 (PD-L1) combined positive score (CPS) >/= 20, CPS >/= 1, and total populations, with no multiplicity or alpha adjustment. RESULTS: The median study follow-up was 45.0 months (interquartile range, 41.0-49.2; n = 882). At data cutoff (February 18, 2020), overall survival improved with pembrolizumab in the PD-L1 CPS >/= 20 (hazard ratio [HR], 0.61; 95% CI, 0.46 to 0.81) and CPS >/= 1 populations (HR, 0.74; 95% CI, 0.61 to 0.89) and was noninferior in the total population (HR, 0.81; 95% CI, 0.68 to 0.97). Overall survival improved with pembrolizumab-chemotherapy in the PD-L1 CPS >/= 20 (HR, 0.62; 95% CI, 0.46 to 0.84), CPS >/= 1 (HR, 0.64; 95% CI, 0.53 to 0.78), and total (HR, 0.71; 95% CI, 0.59 to 0.85) populations. The objective response rate on second-course pembrolizumab was 27.3% (3 of 11). PFS2 improved with pembrolizumab in the PD-L1 CPS >/= 20 (HR, 0.64; 95% CI, 0.48 to 0.84) and CPS >/= 1 (HR, 0.79; 95% CI, 0.66 to 0.95) populations and with pembrolizumab-chemotherapy in the PD-L1 CPS >/= 20 (HR, 0.64; 95% CI, 0.48 to 0.86), CPS >/= 1 (HR, 0.66; 95% CI, 0.55 to 0.81), and total (HR, 0.73; 95% CI, 0.61 to 0.88) populations. PFS2 was similar after pembrolizumab and longer after pembrolizumab-chemotherapy on next-line taxanes and shorter after pembrolizumab and similar after pembrolizumab-chemotherapy on next-line nontaxanes. CONCLUSION: With a 4-year follow-up, first-line pembrolizumab and pembrolizumab-chemotherapy continued to demonstrate survival benefit versus cetuximab-chemotherapy in recurrent/metastatic head and neck squamous cell carcinoma. Patients responded well to subsequent treatment after pembrolizumab-based therapy.
Publisher: American Society of Clinical Oncology
Keywords: Humans; Squamous Cell Carcinoma of Head and Neck/drug therapy; Cetuximab/therapeutic use; *B7-H1 Antigen/metabolism; Neoplasm Recurrence, Local/drug therapy/etiology; *Head and Neck Neoplasms/drug therapy; Antineoplastic Combined Chemotherapy Protocols/therapeutic use
Department(s): Medical Oncology
PubMed ID: 36219809
Publisher's Version: https://doi.org/10.1200/JCO.21.02508
Open Access at Publisher's Site: https://doi.org/10.1200/JCO.21.02508
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2023-05-30 07:27:44

Last Modified: 2023-05-30 07:28:52