KEYNOTE-689
The first new treatment for curable head and neck cancer in six years: immunotherapy around surgery doubled the time patients stayed free of events.
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.
Setting
Resectable stage III-IVA HNSCC: neoadjuvant pembrolizumab, surgery, then adjuvant pembrolizumab with (chemo)radiation vs surgery and (chemo)radiation
Phase
Phase 3
Sponsor
Merck
Registry
Headline result
Median EFS 59.7 vs 29.6 months (CPS ≥1).
Reported
2025
Enrolled
714
Replication
No second phase 3 yet; consistent with neoadjuvant IO benefits in melanoma and lung.
In plain words
What these results mean for people, not percentages
Event-free survival (CPS ≥1)primarysurrogate endpoint
- Median 59.7 vs 29.6 months with Perioperative pembrolizumab compared with Standard of care; about 30.1 months longer for half the group.
- A median is a midpoint: half the people did better than this and half did worse, so it is not a prediction for any one person.
- This is a surrogate endpoint: it measures the cancer being controlled or absent on scans and tests, which often, but not always, translates into living longer.
- These results apply to the people the trial enrolled: Resectable stage III-IVA HNSCC: neoadjuvant pembrolizumab, surgery, then adjuvant pembrolizumab with (chemo)radiation vs surgery and (chemo)radiation. People in a different situation may not see the same effect.
Numbers are from the trial as recorded here; see the source links in the table below. This is orientation, not medical advice: ask your team how closely the trial population matches you.
714 participants enrolled.
| Endpoint | Arm | n | Value | HR (95% CI) | p | Source |
|---|---|---|---|---|---|---|
| Event-free survival (CPS ≥1)primary | Perioperative pembrolizumab | 682 | 59.7 months | — | — | link |
| Standard of care | — | 29.6 months |
Replication
No second phase 3 yet; consistent with neoadjuvant IO benefits in melanoma and lung.