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

Author(s): Kevin J. Harrington, PhD1; Barbara Burtness, MD2; Richard Greil, MD3,4; Denis Soulières, MD5; Makoto Tahara, MD6; Gilberto de Castro Jr, MD7; Amanda Psyrri, MD8; Irene Brana, MD9; Neus Basté, MD9; Prakash Neupane, MD10; Åse Bratland, PhD11; Thorsten Fuereder, MD12; Brett G.M. Hughes, MBBS13; Ricard Mesia, PhD14; Nuttapong Ngamphaiboon, MD15; Tamara Rordorf, MD16; Wan Zamaniah Wan Ishak, MD17; Jianxin Lin, MS18; Burak Gumuscu, MD18; Ramona F. Swaby, MD18; and Danny Rischin, MD19,20
Source: DOI: 10.1200/JCO.21.02508 Journal of Clinical Oncology 41, no. 4 (February 01, 2023) 790-802.
Maem Hussein MD

Dr. Maen Hussein's Thoughts

Pembro with chemotherapy or alone better then cetuximab combination, also improved responses to subsequent therapy.


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.


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.


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.


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.

Author Affiliations

1The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust, National Institute of Health Research Biomedical Research Centre, London, United Kingdom; 2Yale Cancer Center and Yale School of Medicine, New Haven, CT; 3Salzburg Cancer Research Institute-Center for Clinical Cancer and Immunology Trials, Salzburg, Austria; 4Paracelsus Medical University Hospital, and Cancer Cluster Salzburg, Salzburg, Austria; 5Centre Hospitalier de l’Université de Montréal, Montréal, QC, Canada; 6National Cancer Center Hospital East, Kashiwa, Japan; 7Instituto do Cancer do Estado de Sao Paulo, Sao Paulo, Brazil; 8National and Kapodistrian University of Athens, Attikon University Hospital, Athens, Greece; 9Vall d’Hebron University Hospital, Vall d’Hebron Institute of Oncology, Barcelona, Spain; 10University of Kansas Medical Center, Kansas City, KS; 11Oslo University Hospital, Oslo, Norway; 12Medical University of Vienna, Vienna, Austria; 13Royal Brisbane and Women’s Hospital and University of Queensland, Brisbane, QLD, Australia; 14Medical Oncology Department, Catalan Institut of Oncology – Badalona, B-ARGO Group, IGTP, Badalona, Spain; 15Ramathibodi Hospital, Mahidol University, Bangkok, Thailand; 16University Hospital, Zurich, Switzerland; 17Clinical Oncology Unit, Faculty of Medicine, University Malaya, Kuala Lumpur, Malaysia; 18Merck & Co, Inc, Rahway, NJ; 19Peter MacCallum Cancer Centre, Melbourne, VIC, Australia; 20University of Melbourne, Parkville, Melbourne, VIC, Australia

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