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
1
Issued Date
2025-05-15
Resource Type
ISSN
09598049
eISSN
18790852
Scopus ID
2-s2.0-105002856892
Journal Title
European Journal of Cancer
Volume
221
Rights Holder(s)
SCOPUS
Bibliographic Citation
European Journal of Cancer Vol.221 (2025)
Suggested Citation
Tahara M., Greil R., Rischin D., Harrington K.J., Burtness B., de Castro G., Psyrri A., Braña I., Neupane P., Bratland Å., Fuereder T., Hughes B.G.M., Mesía R., Ngamphaiboon N., Rordorf T., Ishak W.Z.W., Lin J., Gumuscu B., Lerman N., Soulières D. 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. European Journal of Cancer Vol.221 (2025). doi:10.1016/j.ejca.2025.115395 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/109806
Title
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
Author's Affiliation
Ramathibodi Hospital
Vall d‘Hebron Institut de Oncologia
Oslo Universitetssykehus
Peter Maccallum Cancer Centre
Universiti Malaya
National and Kapodistrian University of Athens
Royal Brisbane and Women's Hospital
Allgemeines KrankenHaus Wien
UniversitatsSpital Zurich
Yale School of Medicine
Institute Catala Oncologia
Paracelsus Medizinische Privatuniversitat
National Cancer Center Hospital East
The Institute of Cancer Research
Centre Hospitalier de L'Université de Montréal
Universidade de São Paulo
Merck & Co., Inc.
University of Kansas Medical Center
Vall d‘Hebron Institut de Oncologia
Oslo Universitetssykehus
Peter Maccallum Cancer Centre
Universiti Malaya
National and Kapodistrian University of Athens
Royal Brisbane and Women's Hospital
Allgemeines KrankenHaus Wien
UniversitatsSpital Zurich
Yale School of Medicine
Institute Catala Oncologia
Paracelsus Medizinische Privatuniversitat
National Cancer Center Hospital East
The Institute of Cancer Research
Centre Hospitalier de L'Université de Montréal
Universidade de São Paulo
Merck & Co., Inc.
University of Kansas Medical Center
Corresponding Author(s)
Other Contributor(s)
Abstract
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.