How do you approach systemic therapy for a patient with HPV-unrelated recurrent/metastatic head and neck squamous cell carcinoma who has progressed on both a platinum-based regimen and immune checkpoint inhibitor therapy?

I typically look for clinical trials in this space. Thankfully, there are a few options coming up for second line therapy. Outside of a trial, single agents such as cetuximab or capecitabine or docetaxel or MTX have been used with some response rates, but no consistent survival benefit. Therefore where possible, a clinical trial may be reasonable