KEYNOTE-048 Opens Door Farther for Pembrolizumab in Head/Neck Cancer
Posted: Friday, January 3, 2020
A potential new standard of care for treating recurrent or metastatic squamous cell carcinoma of the head and neck is supported by the efficacy and safety results of the phase III, open-label KEYNOTE-048 trial. Pembrolizumab plus platinum and fluorouracil (5-FU) is an appropriate first-line treatment for recurrent or metastatic squamous cell carcinoma of the head and neck, and pembrolizumab monotherapy is a first-line treatment option for patients with PD-L1–positive recurrent or metastatic squamous cell carcinoma of the head and neck, according to a report by Barbara Burtness, MD, of Yale University School of Medicine in New Haven, Connecticut, and colleagues published in The Lancet.
Between 2015 and 2017, the team randomly assigned 882 participants, with about 300 each receiving either pembrolizumab alone; pembrolizumab plus a platinum and 5-FU (pembrolizumab with chemotherapy); or cetuximab plus a platinum and 5-FU (cetuximab with chemotherapy). Patients’ combined positive scores (CPS) represented the degree of PD-L1 present.
Among the key results presented in The Lancet were that at the second interim analysis, pembrolizumab alone improved overall survival versus cetuximab with chemotherapy in the CPS 20+ population (median, 14.9 months vs. 10.7 months; P = .0007) and CPS 1+ population (12.3 vs. 10.3 months; P = .0086) and was noninferior in the total population (11.6 vs. 10.7 months). Pembrolizumab with chemotherapy improved overall survival versus cetuximab with chemotherapy in the total population (13.0 vs. 10.7 months; P = .0034) at the second interim analysis and in the CPS 20+ population (14.7 vs. 11.0 months; P = .0004) and CPS 1+ population (13.6 vs. 10.4 months; P < .0001) at final analysis.
Higher PD-L1 expression is associated with improved response to pembrolizumab, noted Dr. Burtness and co-investigators. “Pembrolizumab monotherapy might be preferred for PD-L1–positive cancers that are associated with a lesser symptom burden, whereas pembrolizumab with chemotherapy might be preferred for patients whose symptom burden indicates a greater importance of objective response or those who have low PD-L1 expression or recurrent-only disease,” they wrote, adding that patient preference will also be important in choosing whether to add chemotherapy or not.
Disclosure: For full disclosures of the study authors, visit thelancet.com.