Immunotherapy, Chemotherapy, or Both: Options for First-Line Therapy for Patients With Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma

The Oncology Grand Rounds series is designed to place original reports published in the Journal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors' suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in the Journal of Clinical Oncology, to patients seen in their own clinical practice.The development of immune checkpoint inhibitors has revolutionized the management of recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC). The landmark KEYNOTE-048 clinical trial established the programmed death-1 inhibitor pembrolizumab with and without chemotherapy as a new standard first-line treatment for patients with platinum-sensitive R/M HNSCC. Nonetheless, clinical decision making can be challenging when considering the significant morbidity associated with rapidly progressive disease in high-risk locations, patient fitness, and programmed death-ligand 1 expression. Both planned and unplanned subgroup analyses from KEYNOTE-048 provide valuable insights into how therapy for untreated R/M HNSCC may be optimized for individual patients. Given differences in the toxicity profile of pembrolizumab alone versus in combination with chemotherapy, prioritizing patient preference is paramount in this palliative treatment setting. Here, the case of a patient presenting with de novo metastatic HNSCC is discussed to highlight the practical application of KEYNOTE-048 data in clinical practice.