The Phase II results of the NRG Oncology HN004 trial indicate that radiotherapy (RT) with the PD-L1 inhibitor durvalumab did not improve progression-free survival (PFS) and led to significantly higher rates of locoregional failure (LRF) when compared to RT + cetuximab in patients with locoregionally advanced head and neck squamous cell carcinoma (HNSCC) that have a contraindication to cisplatin. These findings were presented during the plenary session at American Society for Radiation Oncology (ASTRO) annual meeting held in San Antonio, Texas. This was one of four NRG Oncology papers presented during the 2022 ASTRO plenary session.