# KEYNOTE-689

Source: https://onco.cc/trials/keynote-689/  
OnCo record `keynote-689` (Trial). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

The first new treatment for curable head and neck cancer in six years: immunotherapy around surgery doubled the time patients stayed free of events.

## Summary

Presented AACR April 2025; FDA approval 12 June 2025 for PD-L1 CPS ≥1. In the CPS ≥1 population (n=682), median EFS 59.7 vs 29.6 months. Major pathological response in ~10% of the neoadjuvant arm predicted excellent outcomes. First perioperative approval in HNSCC and the first HNSCC approval since 2019.

## Fields

- Kind: Trial
- Status: positive
- Last checked: 2026-09-07
- Registry id: NCT03765918
- Phase: 3
- Setting: Resectable stage III-IVA HNSCC: neoadjuvant pembrolizumab, surgery, then adjuvant pembrolizumab with (chemo)radiation vs surgery and (chemo)radiation
- Sponsor: Merck
- Enrolled: 714
- Result: Median EFS 59.7 vs 29.6 months (CPS ≥1).
- Outcomes: Event-free survival (CPS ≥1): Perioperative pembrolizumab 59.7 months vs Standard of care 29.6 months
- Replication: No second phase 3 yet; consistent with neoadjuvant IO benefits in melanoma and lung.

## Sources

- ClinicalTrials.gov NCT03765918: https://clinicaltrials.gov/study/NCT03765918
- FDA approval, Merck: https://www.merck.com/news/fda-approves-keytruda-pembrolizumab-for-pd-l1-resectable-locally-advanced-head-neck-squamous-cell-carcinoma-as-neoadjuvant-treatment-continued-as-adjuvant-treatment-combined-with-radiother/

## Connected records

- cancers: [Head and neck squamous cell carcinoma](https://onco.cc/cancers/head-and-neck/), [HPV-negative head and neck squamous cell carcinoma (including HPV-negative oropharyngeal cancer)](https://onco.cc/cancers/hpv-negative-head-and-neck-cancer/), [Hypopharyngeal cancer](https://onco.cc/cancers/hypopharyngeal-cancer/), [Oral tongue and floor of mouth cancer](https://onco.cc/cancers/oral-tongue-cancer/)
- technologies: [IMRT / IGRT (modern external beam)](https://onco.cc/technologies/imrt-igrt/)
- targets: [PD-1](https://onco.cc/targets/pd1/)
- drugs: [Pembrolizumab](https://onco.cc/drugs/pembrolizumab/)
- companies: [Merck & Co. (MSD)](https://onco.cc/companies/merck/)
- terms: [Combined positive score (CPS)](https://onco.cc/terms/cps/), [Event-free / disease-free survival (EFS, DFS, iDFS, RFS)](https://onco.cc/terms/efs/), [Neoadjuvant / adjuvant / perioperative](https://onco.cc/terms/neoadjuvant-adjuvant/)
- people: [Ravindra Uppaluri](https://onco.cc/people/ravindra-uppaluri/)
- pairings: [Immunotherapy before surgery rather than with chemoradiation (HNSCC)](https://onco.cc/pairings/io-before-surgery-hnscc/)
- ideas: [Photoimmunotherapy as an in situ vaccine with PD-1 blockade](https://onco.cc/ideas/idea-photoimmunotherapy-plus-pd1/), [Test one-tenth-dose immunotherapy where the full dose is unaffordable](https://onco.cc/ideas/idea-cost-low-dose-immunotherapy-trials/)
- key papers: [KEYNOTE-689: neoadjuvant and adjuvant pembrolizumab for resectable locally advanced head and neck cancer](https://onco.cc/key-papers/paper-keynote-689-nejm-2025/)
- trials: [NIVOPOSTOP (GORTEC 2018-01)](https://onco.cc/trials/nivopostop/)

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