On August 5, 2016, the U. S. Food and Drug Administration granted accelerated approval to pembrolizumab (Keytruda), an anti–PD-1 (programmed cell death protein 1) therapy, for the treatment of patients with recurrent or metastatic head and neck squamous cell carcinoma with disease progression on or after platinum-containing chemotherapy. The drug was approved at a fixed dose of 200 mg every 3 weeks.
The approval was based on demonstration of a durable objective response rate in a subgroup of patients in an international, multicenter, nonrandomized, open-label, multicohort study. This subgroup included 174 patients with recurrent or metastatic head and neck squamous cell carcinoma who had disease progression on or after platinum-containing chemotherapy. Patients received intravenous pembrolizumab at 10 mg/kg every 2 weeks or 200 mg every 3 weeks.
The objective response rate for these 174 patients was 16% (95% confidence interval, range 11%–22%). The median response duration had not been reached at the time of analysis. The range for duration of response was 2.4 months to 27.7 months (response ongoing). Among the 28 responding patients, 23 (82%) had responses of 6 months or longer.
Safety data were evaluated in 192 patients with head and neck squamous cell carcinoma receiving at least 1 dose of pembrolizumab at 10 mg/kg every 2 weeks or 200 mg every 3 weeks. The most common (≥ 20%) adverse reactions were fatigue, decreased appetite, and dyspnea.
As a condition of the accelerated approval, the drug’s manufacturer, Merck, is required to conduct a multicenter, randomized trial establishing the superiority of pembrolizumab over standard therapy. To that end, Merck’s KEYNOTE-040 trial is ongoing. ■