As reported in the Journal of Clinical Oncology by Laura Q. Chow, MD, of the University of Washington, and colleagues, a fixed-dose reduced-frequency pembrolizumab (Keytruda) regimen produced durable responses in the phase IB KEYNOTE-012 expansion cohort of patients with recurrent or metastatic head and neck squamous cell carcinoma. The response rate was higher among patients with tumor or immune cells positive for the programmed cell death ligand 1 (PD-L1).
In the expansion cohort, 132 patients enrolled irrespective of PD-L1 or human papillomavirus (HPV) status received a fixed dose of pembrolizumab at 200 mg every 3 weeks (compared with 10 mg/kg every 2 weeks in the trial). Patients had a median age of 60 years, 83% were male, 57% had received at least 2 lines of therapy for recurrent/metastatic disease, and 21% had HPV-associated disease.
Responses and Toxicity
On central imaging, the objective response rate among all patients was 18%. The median duration of response was not reached (range = 2+ to 11+ months). The response rate was significantly greater among 84 patients with tumor or immune cells positive for PD-L1 vs 24 patients negative for PD-L1 (22% vs 4%, P = .021). Response rates were 19% vs 16% among patients with tumor cells only positive vs negative for PD-L1. Response rates were 32% in patients with HPV-associated disease and 14% in those without.
Among all patients, 6-month progression-free and overall survival rates were 23% and 59%, respectively. Median overall survival was 303 days in immune/tumor cell PD-L1–positive patients and 151 days in PD-L1–negative patients.
The most common treatment-related adverse events of any grade were fatigue (21%) and hypothyroidism (11%). Grade 3 and 4 adverse events occurred in 6% and 3% of patients.
The investigators concluded: “Fixed-dose pembrolizumab [at] 200 mg administered once every 3 weeks was well tolerated and yielded a clinically meaningful [objective response rate] with evidence of durable responses, which supports further development of this regimen in patients with advanced [head and neck squamous cell carcinoma].”
The study was supported by Merck.