New Immunotherapy Strategy Improves Outcomes in Patients with Advanced Head and Neck Cancer
A new study shows that adding pembrolizumab to standard surgery and radiation treatments significantly improves outcomes for patients with newly diagnosed, locally advanced head and neck squamous cell carcinoma. Results of the phase 3 trial were presented at the 2025 American Association for Cancer Research Annual Meeting.
The KEYNOTE-689 study, led by researchers at the Brigham and Women’s Hospital and the Dana-Farber Brigham Cancer Center, looked at the use of perioperative pembrolizumab, given both before and after surgery, alongside standard care. The trial enrolled 714 patients with stage 3 or 4 locally advanced head and neck squamous cell carcinoma affecting the larynx, hypopharynx and oral cavity. Half of the patients received pembrolizumab in addition to surgery and pathology-directed adjuvant therapy.
After a median follow-up of more than three years, patients treated with pembrolizumab were at least 27% less likely to experience cancer recurrence or death compared to those receiving standard care alone.
The addition of pembrolizumab also boosted the major pathologic response rate, indicating significant tumor shrinkage prior to surgery, particularly in patients whose tumors expressed high levels of PD-L1, a protein found on the surface of cancer cells that acts like a shield to help cells avoid being attacked by the immune system.
Drugs like pembrolizumab are called immune checkpoint inhibitors. They’re designed to block PD-1 or PD-L1. Blocking this connection releases the brakes on the immune system, letting T cells recognize and attack the cancer.
Kedar Kirtane, MD
“The use of neoadjuvant and possibly adjuvant pembrolizumab in patients with head and neck cancer will evolve over time,” said Kedar Kirtane, MD, a medical oncologist in the Head and Neck-Endocrine Oncology Department at Moffitt Cancer Center. “This is the first step in what is likely a flurry of studies assessing this strategy. Time will tell whether this will truly change standard of care.”
Safety outcomes showed that rates of severe treatment-related adverse events were similar between groups, though immune-mediated side effects such as hypothyroidism were more common in the pembrolizumab group. There were four deaths linked to treatment in the pembrolizumab arm compared to one in the control group.
The study did not separate the individual contributions of pre and postsurgery pembrolizumab treatment to the overall positive results. Further research is planned to refine this new approach, with the goal of enhancing benefits while minimizing treatment-related side effects.
