The treatment landscape for recurrent or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) has undergone a significant transformation in recent years, thanks to the emergence of immunotherapies. Pembrolizumab, an anti-PD-1 antibody, has been approved as monotherapy or in combination with chemotherapy for patients with R/M HNSCC whose tumors express programmed death ligand 1 (PD-L1) at a combined positive score (CPS) of 1 or higher.

The KEYNOTE-048 trial, published recently, has further solidified the role of pembrolizumab in the treatment of R/M HNSCC. In this phase III randomized trial, pembrolizumab was shown to be superior to the EXTREME regimen (cis- or carboplatin, 5-fluorouracil (5-FU), and cetuximab) in all patients with R/M HNSCC, regardless of PD-L1 expression. Moreover, pembrolizumab monotherapy was found to be superior to chemotherapy alone in patients whose tumors express PD-L1.

These findings are consistent with the results of two other phase III randomized trials, which demonstrated that anti-PD-1 antibodies such as nivolumab and pembrolizumab were superior to investigator's choice chemotherapy in second-line platinum-refractory R/M HNSCC. Collectively, these studies have conclusively proven that exposure to a PD-1 inhibitor prolongs survival in patients with R/M HNSCC.

The use of PD-L1 biomarker testing will play a crucial role in guiding treatment decisions for patients with R/M HNSCC. A scoring system known as the combined positive score (CPS) is used to assess PD-L1 expression, which incorporates immune cell staining. This test will be routinely used to inform treatment choices until more detailed clinical data are available.

In conclusion, the KEYNOTE-048 trial has significantly expanded our understanding of the role of pembrolizumab in the treatment of R/M HNSCC. With its proven efficacy and tolerability, pembrolizumab is now a valuable option for patients with this aggressive disease, particularly those whose tumors express PD-L1. As we continue to explore the potential benefits of immunotherapies in HNSCC, it is clear that these agents will play a critical role in improving outcomes for patients with this devastating disease.

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