In a phase II trial reported in the Journal of Clinical Oncology, Zandberg et al compared sequential vs concurrent pembrolizumab with chemoradiotherapy (CRT) in patients with locally advanced head and neck squamous cell carcinoma.
Study Details
In the U.S. multicenter noncomparative trial, 80 patients were randomly assigned between 2016 and 2021 to receive concurrent pembrolizumab at 200 mg every 3 weeks x 8 starting 1 week before CRT with cisplatin at 40 mg/m2 once weekly plus radiation therapy at 70 Gy (n = 41) or sequential pembrolizumab starting 2 weeks after CRT at the same dosages. The decision to select a treatment regimen for advancement to a larger trial was based on trivariate endpoints: dose-limiting toxicity, 1-year locoregional failure rate, and 1-year progression-free survival. If both treatment groups met the criteria, the regimen of the group with numerically better 1-year progression-free survival would be selected for advancement.
Key Findings
Overall, 71% of patients had oropharyngeal disease, and 92.5% had stage IV disease.
Both groups met the trivariate endpoint criteria. The sequential group had better 1-year progression-free survival (84% vs 71%). The 4-year outcomes at least numerically favored the sequential group: locoregional control was 96% vs 64% (hazard ratio [HR] = 0.11, 95% confidence interval [CI] = 0.01–0.89, P = .012); the progression-free survival rate was 69% vs 49% (HR = 0.55, 95% CI = 0.25–1.22, P = .132); and the overall survival rate was 83% vs 71% (HR = 0.51, 95% CI = 0.19–1.37, P = .17).
A significant increase in macrophages, PD-L1–positive macrophages, and PD-L1–positive tumor cells was observed with treatment in the concurrent group but not in the sequential group.
The investigators concluded: “CRT with sequential pembrolizumab met criteria for further study. Immunosuppressive changes in the [tumor microenvironment] differed between arms, reflecting the impact of one dose of pembrolizumab in the concurrent arm.”
Robert L. Ferris, MD, PhD, of UNC Lineberger Comprehensive Cancer Center, Chapel Hill, is the corresponding author of the Journal of Clinical Oncology article.
Disclosure: This study was supported by Merck through the Merck investigator studies program and the National Cancer Institute. For full disclosures of all study authors, visit the Journal of Clinical Oncology.
