EA3191 – A Phase II Randomized Trial of Adjuvant Therapy with Pembrolizumab after Resection of Recurrent/Second Primary Head and Neck Squamous Cell Carcinoma with High Risk Features

For patients with resectable, locoregionally recurrent or second primary head and neck squamous cell carcinoma (HNSCC) in a previously irradiated field, surgery is the standard of care. Unfortunately, resection outcomes are poor, with a two-year overall survival rate of 30% - 60%. A prior study explored adjuvant treatment with re-irradiation plus concurrent chemotherapy; this yielded improvement in disease-free survival but no change in overall survival compared to observation. Additionally, this approach caused significant toxicity. As a result, oncologists typically reserve this option for patients whose disease has high-risk features.

EA3191 aims to find better options for this patient population. To be eligible for this trial, patients must be adults with locoregionally recurrent or second primary HNSCC in a previously radiated field. They must have undergone surgery with gross total resection within eight weeks of randomization—and they must have high-risk disease. Other eligibility criteria apply.

After surgery, study participants with high-risk features, e.g., positive margins and/or extranodal extension, will be randomized 1:1:1 across three study groups. Arm A will receive re-irradiation plus pembrolizumab, an anti-PD-1 monoclonal antibody. Arm B will receive re-irradiation plus chemotherapy. Arm C will receive pembrolizumab alone.

Anti-PD-1 therapy has shown promise in other studies—both in HNSCC and in other cancer types—and pembrolizumab is already FDA-approved for HNSCC in certain settings. Investigators believe the two treatment arms that include pembrolizumab will each demonstrate significantly improved overall survival compared to the re-irradiation/chemotherapy arm.

This study is led by Dan P. Zandberg, MD (University of Pittsburgh).

Learn more about EA3191 at ecog-acrin.org.