Fig. 1

Treatment Algorithm 1: First-line treatment for R/M HNSCC patients. Immunotherapy treatment algorithm for R/M Systemic Therapy Naïve HNSCC. This treatment strategy takes into account recent data from the Keynote-048 trial and would be reasonable if pembrolizumab is available. All treatment options shown may be appropriate. The final selection of therapy should be individualized based on patient eligibility and therapy availability based on the treating physician’s discretion. The goal of these algorithms are to provide advice as the consensus recommendations of the Subcommittee. 1) Treating physician will determine if patient is fit to undergo pembrolizumab monotherapy or pembrolizumab/cisplatin/5-FU combination therapy as first-line therapy for R/M HNSCC. 2) If patient experiences disease progression on or after pembrolizumab monotherapy, patient should receive platinum based chemotherapy or be enrolled in an appropriate clinical trial. 3) If patient experiences disease progression on or after pembrolizumab/cisplatin/5-FU combination therapy, patient may receive second-line non-platinum based chemotherapy/cetuximab or be enrolled in an appropriate clinical trial. In addition, patients are eligible for nivolumab or pembrolizumab regardless of PD-L1 expression, according to the 2016 FDA approvals of nivolumab and pembrolizumab for second-line treatment of patients with HNSCC. *Clinical trials, including those that are immunotherapy-based, should be considered in all HNSCC patients, in all lines of therapy