Window-of-opportunity clinical trials for biomarker discovery in head and neck squamous cell carcinoma

Purpose of review: We review the window-of-opportunity clinical trials that have been reported in head and neck squamous cell carcinoma (HNSCC), and discuss their challenges.

Recent findings: Limited treatment options exist in HNSCC. Cetuximab, an mAb targeting epidermal growth factor receptor, and the PD-1 inhibitors nivolumab and pembrolizumab, are the only drugs that improved overall survival in the recurrent and/or metastatic setting. Both cetuximab and nivolumab improve overall survival by less than 3 months, potentially because of the lack of predictive biomarkers. The only validated predictive biomarker to date is protein ligand PD-L1 expression that predicts the efficacy of pembrolizumab in first-line, nonplatinum refractory recurrent and/or metastatic HNSCC. The identification of biomarkers of efficacy of new drugs is key to avoid administering toxic drugs to patients who will not benefit from them, and to expect increased drug efficacy in the biomarker-positive group of patients. One way of identifying such biomarkers are the window-of-opportunity trials in which drugs are given for a short period of time before the definitive treatment, with the aim to collect samples for translational research. These trials differ from neoadjuvant strategies where efficacy is the primary endpoint.

Summary: We show that these trials were safe and successful in identifying biomarkers.