As reported in the Journal of Clinical Oncology by Kevin Harrington, MD, PhD, and colleagues, updated results of the phase III KEYNOTE-048 trial showed enduring survival benefits with first-line pembrolizumab alone and pembrolizumab/chemotherapy vs cetuximab/chemotherapy in patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC).
The trial supported the June 2019 approval of pembrolizumab monotherapy in patients with a PD-L1 combined positive score (CPS) ≥ 1 or pembrolizumab in combination with platinum/fluorouracil in the first-line treatment of unresectable recurrent or metastatic HNSCC.
Kevin Harrington, MD, PhD
Study Details
In the open-label trial, 882 patients were randomly assigned 1:1:1 to receive pembrolizumab alone (n = 301), pembrolizumab plus platinum/fluorouracil chemotherapy (n = 281), or cetuximab plus platinum/fluorouracil chemotherapy (n = 300). Efficacy was evaluated in the CPS ≥ 20, CPS ≥ 1, and total populations.
Key Findings
Median follow-up was 45.0 months (interquartile range = 41.0–49.2 months). Compared with cetuximab/chemotherapy, overall survival was improved with pembrolizumab in the CPS ≥ 20 population (hazard ratio [HR] = 0.61, 95% confidence interval [CI] = 0.46–0.81) and CPS ≥ 1 population (HR = 0.74, 95% CI = 0.61–0.89) and was noninferior in the total population (HR = 0.81, 95% CI = 0.68–0.97). Compared with cetuximab/chemotherapy, overall survival was improved with pembrolizumab/chemotherapy in the CPS ≥ 20 population (HR = 0.62, 95% CI = 0.46–0.84), CPS ≥ 1 population (HR = 0.64, 95% CI = 0.53–0.78), and total population (HR = 0.71, 95% CI = 0.59–0.85).
Compared with the cetuximab/chemotherapy group, progression-free survival–2 among patients receiving subsequent therapy was improved in the pembrolizumab group in the CPS ≥ 20 population (HR = 0.64, 95% CI = 0.48–0.84) and CPS ≥ 1 population (HR = 0.79, 95% CI = 0.66–0.95), and in the pembrolizumab/chemotherapy group in the CPS ≥ 20 (HR = 0.64, 95% CI = 0.48–0.86), CPS ≥ 1 (HR = 0.66, 95% CI = 0.55–0.81), and total populations (HR = 0.73, 95% CI = 0.61–0.88). Overall, progression-free survival–2 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.
The investigators concluded, “With a 4-year follow-up, first-line pembrolizumab and pembrolizumab/chemotherapy continued to demonstrate survival benefit vs cetuximab/chemotherapy in recurrent or metastatic HNSCC. Patients responded well to subsequent treatment after pembrolizumab-based therapy.”
Dr. Harrington, of The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust, London, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by Merck Sharp & Dohme LLC, a subsidiary of Merck & Co, Inc. For full disclosures of the study authors, visit ascopubs.org.
