Abstract
Pembrolizumab is well tolerated and active in advanced squamous cell carcinoma of the head and neck.
Major finding: Pembrolizumab is well tolerated and active in advanced squamous cell carcinoma of the head and neck.
Clinical relevance: Greater activity was associated with increased expression of PD-L1 and a panel of IFNγ-related genes.
Impact: Pembrolizumab warrants further investigation in patients with PD-L1–positive head and neck tumors.
Pembrolizumab is a humanized monoclonal antibody targeting programmed death 1 (PD-1) that is approved for the treatment of melanoma and has shown efficacy in multiple advanced solid tumor types. In preclinical studies, PD-1 blockade promoted antitumor activity in squamous cell carcinoma of the head and neck, prompting Seiwert and colleagues to evaluate the safety and clinical activity of pembrolizumab in a phase Ib, open-label, multicenter trial of 60 patients with PD-L1–positive recurrent or metastatic squamous cell carcinoma of the head and neck. In total, 23 patients were human papillomavirus (HPV)–positive, and 37 were HPV-negative. The primary endpoints were safety and the proportion of patients who achieved an overall response; secondary endpoints included response based on HPV status, response duration, and progression-free and overall survival. Expression of six IFNγ-related genes identified as predictive biomarkers of pembrolizumab response in melanoma was also assessed. Pembrolizumab was well tolerated and safe; treatment-related adverse events occurred in 63% of patients and most commonly included fatigue, pruritus, and rash. The most common grade 3–4 adverse events were alanine aminotransferase or aspartate aminotransferase increases and hyponatremia, each occurring in 2 patients. Central imaging review confirmed an overall response in 8 (18%) of 45 evaluable patients, including 1 complete response and 7 partial responses, as well as stable disease in 8 patients. The overall response rate was 25% in HPV-positive patients and 14% in HPV-negative patients, and 51% of patients experienced a reduction in tumor burden. The median response duration was 53 weeks and median overall survival was 13 months. Higher expression of PD-L1 and the six IFNγ-related genes was detected in responding patients compared to nonresponding patients. Altogether, this study suggests that pembrolizumab is safe, well tolerated, and exhibits antitumor activity in patients with advanced squamous cell carcinoma of the head and neck, and supports further clinical investigation of pembrolizumab in larger clinical trials.
Note: Research Watch is written by Cancer Discovery editorial staff. Readers are encouraged to consult the original articles for full details. For more Research Watch, visit Cancer Discovery online at http://cancerdiscovery.aacrjournals.org/content/early/by/section.
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