Immunotherapy has transformed the care of patients with recurrent/metastatic head and neck cancer but integration into definitive management has been more challenging. There are recent clinical trials investigating immunotherapy/radiation combinations for patients with locally advanced head and neck cancer. It is imperative that radiation oncology professionals remain current in state of the art data regarding radiation/immunotherapy combinations. This activity discusses recent efforts to use immunotherapy before, during and after radiation in an attempt to improve cure rates and reduce toxicity. These data include recent potential practice changing clinical trials such as Keynote 689, as well as more novel and experimental approaches. This activity also provides participants the opportunity to gain exposure to the latest data regarding radiation/immunotherapy combinations as they apply to the definitive management of patients with head and neck cancer.  

We examine the evolving landscape of therapeutic de-escalation for HPV-related oropharyngeal cancer. We discuss key recently completed de-escalation trials and discuss innovative FMISO-based biomarker strategies aimed at identifying patients who may benefit from reduced-intensity therapy while maintaining optimal outcomes. Subsequently,
this webinar focuses on the role of immunotherapy in definitive head and neck cancer management. We provide in-depth analysis of pivotal trials including KEYNOTE-689, which explores perioperative pembrolizumab in resectable head and neck squamous cell carcinoma, and NIVOPOSTOP, investigating adjuvant nivolumab following postoperative
chemoradiotherapy. These landmark studies are defining new standards for integrating immune checkpoint inhibitors into curative-intent treatment protocols.

The past several decades have brought significant advances in the management of head and neck cancer. Chief among these has been the recognition of HPV-mediated oropharyngeal cancer as a distinct disease entity, reshaping treatment paradigms and clinical-decision making. As outcomes for this patient population have improved, increasing attention has been directed toward strategies that maintain oncologic efficacy while reducing long-term treatment-related toxicity. This has led to the development and evaluation of de-escalated therapeutic approaches across surgical, radiation and systemic treatment modalities. In the second part of this presentation, we provide an overview of the current landscape of de-escalated therapies in HPV-mediated oropharyngeal cancer, including a review of key prospective and randomized clinical trials. We examine areas of therapeutic success and failure, discuss lessons learned from recent studies, and consider ongoing challenges in patient selection and treatment optimization. Finally, we highlight future directions and emerging innovations, including biomarker-driven approaches and novel trial designs, that may further refine treatment paradigms and improve quality of life for patients. 

Topics:

1. Immunotherapy in Definitive Treatment of Head and Neck Cancer
   Jonathan Schoenfeld, MD, MPH
2. Therapeutic De-escalation for HPV+ Oropharyngeal Cancer
   Christopher Wilke, MD, PhD
3. Q and A
   Yvonne Mowery, MD - Moderator
   Jonathan Schoenfeld, MD, MPH
   Christopher Wilke, MD, PhD

This activity was presented as a live webinar on February 26, 2026. The activity is available from March 3, 2026 through 11:59 am Eastern time on March 2, 2028.