Fulltext

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 1 , Burtness B 2 , Greil R 3 , Soulières D 4 , Tahara M 5 , de Castro G 6 Show all authors , Psyrri A 7 , Brana I 8 , Basté N 8 , Neupane P 9 , Bratland Å 10 , Fuereder T 11 , Hughes BGM 12 , Mesia R 13 , Ngamphaiboon N 14 , Rordorf T 15 , Wan Ishak WZ 16 , Lin J 17 , Gumuscu B 17 , Swaby RF 17 , Rischin D 18

Affiliations 

  • 1 The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust, National Institute of Health Research Biomedical Research Centre, London, United Kingdom
  • 2 Yale Cancer Center and Yale School of Medicine, New Haven, CT
  • 3 Salzburg Cancer Research Institute-Center for Clinical Cancer and Immunology Trials, Salzburg, Austria
  • 4 Centre Hospitalier de l'Université de Montréal, Montréal, QC, Canada
  • 5 National Cancer Center Hospital East, Kashiwa, Japan
  • 6 Instituto do Cancer do Estado de Sao Paulo, Sao Paulo, Brazil
  • 7 National and Kapodistrian University of Athens, Attikon University Hospital, Athens, Greece
  • 8 Vall d'Hebron University Hospital, Vall d'Hebron Institute of Oncology, Barcelona, Spain
  • 9 University of Kansas Medical Center, Kansas City, KS
  • 10 Oslo University Hospital, Oslo, Norway
  • 11 Medical University of Vienna, Vienna, Austria
  • 12 Royal Brisbane and Women's Hospital and University of Queensland, Brisbane, QLD, Australia
  • 13 Medical Oncology Department, Catalan Institut of Oncology - Badalona, B-ARGO Group, IGTP, Badalona, Spain
  • 14 Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
  • 15 University Hospital, Zurich, Switzerland
  • 16 Clinical Oncology Unit, Faculty of Medicine, University Malaya, Kuala Lumpur, Malaysia
  • 17 Merck & Co, Inc, Rahway, NJ
  • 18 Peter MacCallum Cancer Centre, Melbourne, VIC, Australia
J Clin Oncol, 2023 Feb 01;41(4):790-802.
PMID: 36219809 DOI: 10.1200/JCO.21.02508

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.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

MeSH terms
Similar publications