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.

Conflict of interest statement

Authors’ disclosures of potential conflicts of interest are found in the article online at www.jco.org. Author contributions are found at the end of this article.

Figures

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).