KEYNOTE 689

ASCO 2025 featured the presentation of updated results of the randomised, phase 3 KEYNOTE-689 trial, which tested the addition of pembrolizumab to standard care for patients with resectable locally advanced head and neck cancer. 

The global trial enrolled over 700 patients who were randomised to receive either standard care, which included surgery and radiation, or standard care plus pembrolizumab. Pembrolizumab was administered for two cycles before surgery and 15 cycles after surgery.

The primary endpoint of the trial, event-free survival, showed a significant improvement in the pembrolizumab group. The combination of pembrolizumab and standard care resulted in a 27% reduction in the risk of death or disease recurrence compared to standard care alone. The side effect profile of the combination was tolerable, with no negative impact on the ability to proceed with surgery, radiation, or chemo-radiation. In fact, patients receiving pembrolizumab experienced fewer side effects, including a lower risk of neutropenia and radiation-induced dermatitis.

Overall, this trial provides high-level evidence that the addition of neoadjuvant pembrolizumab before and adjuvant pembrolizumab after standard care should become the new standard of care for treating patients with locally resectable head and neck cancer.