Antitumor Activity of Pembrolizumab in Biomarker-Unselected Patients With Recurrent and/or Metastatic Head and Neck Squamous Cell Carcinoma: Results From the Phase Ib KEYNOTE-012 Expansion Cohort

Abstract

Purpose Treatment with pembrolizumab, an anti-programmed death-1 antibody, at 10 mg/kg administered once every 2 weeks, displayed durable antitumor activity in programmed death-ligand 1 (PD-L1) -positive recurrent and/or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) in the KEYNOTE-012 trial. Results from the expansion cohort, in which patients with HNSCC, irrespective of biomarker status, received a fixed dose of pembrolizumab at a less frequent dosing schedule, are reported. Patients and Methods Patients with R/M HNSCC, irrespective of PD-L1 or human papillomavirus status, received pembrolizumab 200 mg intravenously once every 3 weeks. Imaging was performed every 8 weeks. Primary end points were overall response rate (ORR) per central imaging vendor (Response Evaluation Criteria in Solid Tumors v1.1) and safety. Secondary end points included progression-free survival, overall survival, and association of response and PD-L1 expression. Patients who received one or more doses of pembrolizumab were included in analyses. Results Of 132 patients enrolled, median age was 60 years (range, 25 to 84 years), 83% were male, and 57% received two or more lines of therapy for R/M disease. ORR was 18% (95% CI, 12 to 26) by central imaging vendor and 20% (95% CI, 13 to 28) by investigator review. Median duration of response was not reached (range, ≥ 2 to ≥ 11 months). Six-month progression-free survival and overall survival rates were 23% and 59%, respectively. By using tumor and immune cells, a statistically significant increase in ORR was observed for PD-L1-positive versus -negative patients (22% v 4%; P = .021). Treatment-related adverse events of any grade and grade ≥ 3 events occurred in 62% and 9% of patients, respectively. Conclusion Fixed-dose pembrolizumab 200 mg administered once every 3 weeks was well tolerated and yielded a clinically meaningful ORR with evidence of durable responses, which supports further development of this regimen in patients with advanced HNSCC.

Trial registration: ClinicalTrials.gov NCT01848834.

Fig 1.

Consort diagram. Patient disposition. AE, adverse event; PD, progressive disease.

Fig 2.

Efficacy of pembrolizumab on the basis of RECIST (v1.1; Response Evaluation Criteria in Solid Tumors) by central imaging vendor review. (A) Maximum percentage change from baseline in target lesions. Includes patients who had a comparable number of lesions between baseline and postbaseline scans (n = 96). (B) Treatment exposure and response duration in responders (all responders, n = 24). (C and D) Kaplan-Meier estimates of (C) progression-free survival and (D) overall survival (all-patients-as-treated population, N = 132). CR, complete response; PD, progressive disease; PR, partial response.

Fig 3.

(A) Association of efficacy and programmed death-ligand 1 (PD-L1) expression. Overall response by PD-L1 expression in tumor and immune cells and tumor cells alone. (B and C) Kaplan-Meier estimates of (B) progression-free survival (PFS) and (C) overall survival (OS) on the basis of a positive expression cutoff of ≥ 1% in tumor and immune cells (all-patients-as-treated population, N = 132).