(HealthDay News) — The checkpoint inhibitor pembrolizumab prolongs survival in patients with certain head and neck cancers, according to a phase 3 study published online Oct. 31 in The Lancet.
Barbara Burtness, M.D., from the Yale University School of Medicine in New Haven, Connecticut, and colleagues characterized patients with untreated locally incurable recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) by programmed death ligand 1 (PD-L1) expression, p16 status, and performance status. Patients were then randomly assigned (1:1:1) to pembrolizumab alone (301 patients), pembrolizumab plus a platinum and 5-fluorouracil (pembrolizumab with chemotherapy; 281 patients), or cetuximab plus a platinum and 5-fluorouracil (cetuximab with chemotherapy; 300 patients).
The researchers found that at the second interim analysis, pembrolizumab alone improved overall survival versus cetuximab with chemotherapy among patients with a combined positive score (CPS) of 20 or more population (median, 14.9 versus 10.7 months; hazard ratio [HR], 0.61; 95 percent confidence interval [CI], 0.45 to 0.83; P = 0.0007) and CPS of 1 or more population (12.3 versus 10.3; HR, 0.78; 95 percent CI, 0.64 to 0.96; P = 0.0086). For the entire study population, pembrolizumab was noninferior (HR, 0.85; 95 percent CI, 0.71 to 1.03; P = 0.0456). Compared with cetuximab with chemotherapy, pembrolizumab with chemotherapy improved overall survival in the total population (13 versus 10.7 months; HR, 0.77; 95 percent CI, 0.63 to 0.93; P = 0.0034), as well as in the CPS of ≥20 group (14.7 versus 11; HR, 0.60; 95 percent CI, 0.45 to 0.82; P = 0.0004) and CPS of ≥1 group (13.6 versus 10.4; HR, 0.65; 95 percent CI, 0.53 to 0.80; P < 0.0001) at final analysis. At the second interim analysis, neither pembrolizumab alone nor with chemotherapy improved progression-free survival. At final analysis, grade 3 or worse all-cause adverse events occurred in 55 percent of 300 treated participants in the pembrolizumab-alone group, 85 percent of 276 in the group receiving pembrolizumab with chemotherapy, and 83 percent of 287 group receiving cetuximab with chemotherapy.
“Based on the observed efficacy and safety, pembrolizumab plus platinum and 5-fluorouracil is an appropriate first-line treatment for recurrent or metastatic HNSCC and pembrolizumab monotherapy is an appropriate first-line treatment for PD-L1-positive recurrent or metastatic HNSCC,” the authors write.
Several authors disclosed financial ties to pharmaceutical companies, including Merck, which manufactures pembrolizumab and funded the study.