Pembrolizumab in the first-line treatment of advanced head and neck cancer

Introduction Recurrent or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) is associated with dismal prognosis and has limited therapeutic options. PD-1/PD-L1 axis blockade was initially shown to improve outcomes in platinum-refractory HNSCC. More recently, pembrolizumab monotherapy or pembrolizumab combined with chemotherapy resulted in better overall survival than platinum, 5-fluorouracil, and cetuximab (EXTREME regimen) as first-line therapy for R/M HNSCC, establishing a new standard-of-care therapy for this disease. Areas covered We review pembrolizumab in the first-line treatment of R/M HNSCC and summarize the impact of PD-L1 expression, tumor and symptom burden, and patient's performance status on treatment decisions. Future perspectives are summarized. Expert opinion The standard-of-care first-line therapy for R/M HNSCC is pembrolizumab monotherapy for patients with a PD-L1 combined positive score (CPS)>= 1 or pembrolizumab combined with platinum and 5-fluorouracil for patients with any PD-L1 status. Addition of chemotherapy to pembrolizumab increases the response rate but also toxicity and is preferred for patients with good performance status and significant tumor and symptom burden. For patients with a PD-L1 CPS <1, the EXTREME regimen should be considered. New strategies combining pembrolizumab with targeted therapies and immune checkpoints inhibitors are being explored to synergize or overcome resistance to anti-PD-1.

Automated summary

Pembrolizumab has shown promising results in first-line treatment of R/M HNSCC, with considerations of PD-L1 expression, tumor and symptom burden, and patient's performance status impacting treatment decisions. Future strategies include exploring combinations of pembrolizumab with targeted therapies and immune checkpoint inhibitors to enhance effectiveness and overcome resistance.