FDA Approves Standard-Changing Therapy Trialed at Siteman

Immunotherapy Improves Survival of Patients with Locally Advanced Head and Neck Cancer

The Food and Drug Administration (FDA) has approved a new standard of care for certain locally advanced head and neck cancers — the first change in standard-of-care therapy for affected patients in more than two decades. This follows the promising results of clinical trials first launched at Siteman Cancer Center at Barnes-Jewish Hospital and WashU Medicine in 2013.

The drug, pembrolizumab (brand name Keytruda), has revolutionized care for melanoma since it was first introduced more than a decade ago. On June 12, 2025, the FDA approved the immunotherapy as part of a new standard of care for certain adults with resectable locally advanced head and neck squamous cell carcinoma (HNSCC).

An international phase 3 clinical trial co-led by WashU Medicine physician-scientists at Siteman showed that such patients benefited from the addition of the immunotherapy drug to the previous standard-of-care therapy. They saw greater tumor shrinkage prior to surgery and, on average, survived cancer-free almost two years longer than did patients who received only the previous standard of care.

“It’s exciting to see our ideas move toward clinical practice with such impressive and potentially life-changing results,” said Douglas R. Adkins, MD, a professor of medicine and director of the Section of Head and Neck and Thyroid Medical Oncology at WashU Medicine who has co-led the clinical trials at Siteman and elsewhere.

Head and neck cancers include tumors of the mouth, sinuses, nose and throat. Smoking and other tobacco use as well as human papillomavirus (HPV) infection increase the risk of such cancers.

Specifically, affected patients are those with resectable locally advanced HNSCC whose tumors express PD-L1 [Combined Positive Score (CPS) ≥1] as determined by an FDA-approved test, as a single agent as neoadjuvant treatment, continued as adjuvant treatment in combination with radiotherapy (RT) with or without cisplatin after surgery, and then as a single agent.

Pembrolizumab is what’s known as an immune checkpoint inhibitor, meaning that it works by skirting roadblocks that keep the body’s own immune cells from destroying tumor cells. One of these roadblocks is a protein on the surface of tumors called PD-L1. By circumventing PD-L1, pembrolizumab allows the patient’s own immune cells to attack and kill tumor cells. The FDA approved the therapy for advanced melanoma in 2014. It has since been approved for many other cancers, including advanced lung cancer, colorectal cancer, cervical cancer and lymphoma. In 2016, it was approved for recurrent and metastatic head and neck cancer.

The proposal to evaluate pembrolizumab in locally advanced head and neck cancer originated at WashU Medicine and formed the basis of an earlier phase 2 clinical trial that began at Siteman in 2013. The findings from that study led directly to the international phase 3 trial that the FDA considered in its recent approval.

The FDA decision also was the first approval of a therapy for HNSCC in six years and the first overall perioperative approval for locally advanced HNSCC.

“The survival benefit we’ve seen in adding pembrolizumab to the previous standard-of-care therapy is clinically meaningful and groundbreaking,” said Adkins, who treats patients at the Robert Ebert and Greg Stubblefield Head & Neck Tumor Center, which he co-leads at Siteman.

He reported findings from the international phase 3 clinical trial, funded by Merck, at this year’s annual meeting of the American Society of Clinical Oncology (ASCO). His co-investigator, Ravindra Uppaluri, MD, PhD, of Dana-Farber Brigham Cancer Center, presented related findings at the American Association for Cancer Research (AACR) annual meeting.