# KEYNOTE-689: neoadjuvant and adjuvant pembrolizumab for resectable locally advanced head and neck cancer

Source: https://onco.cc/key-papers/paper-keynote-689-nejm-2025/  
OnCo record `paper-keynote-689-nejm-2025` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Giving pembrolizumab before surgery and continuing it afterwards alongside radiotherapy reduced recurrences in resectable locally advanced head and neck cancer, the first improvement in surgical treatment of the disease in two decades.

## Summary

Phase 3 trial of 714 patients with resectable stage III to IVA head and neck squamous cell carcinoma (excluding HPV-positive oropharynx in most analyses) randomised to two cycles of neoadjuvant pembrolizumab followed by surgery and adjuvant pembrolizumab with radiotherapy or chemoradiotherapy, or surgery and adjuvant radiotherapy or chemoradiotherapy alone.

Event-free survival was improved in patients with a PD-L1 combined positive score of 10 or more (median 59.7 versus 26.9 months; hazard ratio 0.66) and of 1 or more (hazard ratio 0.70), and major pathological responses occurred in 9.3 percent after neoadjuvant treatment.

## Fields

- Kind: Key paper
- Last checked: 2026-09-17
- Journal: New England Journal of Medicine
- Year: 2025
- DOI: 10.1056/NEJMoa2415434
- Authors: Uppaluri R, Haddad RI, Tao Y, et al.
- Findings: Combined positive score 10 or more: median event-free survival 59.7 vs 26.9 months; hazard ratio 0.66.; Combined positive score 1 or more: hazard ratio 0.70.
- What it means: Perioperative pembrolizumab is a new standard for resectable head and neck cancer with PD-L1 expression, adding immunotherapy to a treatment pathway that had not changed since postoperative chemoradiation was defined.
- Caveats: Overall survival data immature.; Pembrolizumab was continued for up to 15 cycles after surgery, adding cost and immune toxicity.

## Sources

- N Engl J Med 2025: https://doi.org/10.1056/NEJMoa2415434
- PubMed: https://pubmed.ncbi.nlm.nih.gov/40532178/

## Connected records

- cancers: [HPV-negative head and neck squamous cell carcinoma (including HPV-negative oropharyngeal cancer)](https://onco.cc/cancers/hpv-negative-head-and-neck-cancer/)
- drugs: [Pembrolizumab](https://onco.cc/drugs/pembrolizumab/)
- trials: [KEYNOTE-689](https://onco.cc/trials/keynote-689/)
- journals: [New England Journal of Medicine](https://onco.cc/journals/nejm/)

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