The news at a glance
- This study was in patients with head and neck cancer (mouth, throat, voice box) whose tumour was large but could be removed with surgery [1].
- Adding the immunotherapy drug pembrolizumab before and after surgery kept more patients free of the cancer coming back for up to 3 years: about one more patient in every 10, especially when the tumour's PD-L1 test was high [1].
- Giving the drug before surgery did not delay surgery or make it impossible [1].
- This treatment was approved in the US in June 2025; the first new treatment for these patients in about two decades [2].
- Overall survival: how long patients lived.
- Progression-free survival: how long the disease did not get worse.
- Disease-free or event-free survival: how long the disease did not come back after treatment.
- Median: the number that half of patients were above and half below; for example, "a median of 10 months" means that in half of patients the disease stayed under control for at least 10 months.
- Phase 3: a large, careful study comparing a new drug with the usual treatment; the basis of most approvals.
Talk to your doctor about what this result means for you.
What does this finding mean for patients?
If your head and neck cancer can be removed with surgery, ask your doctor whether a PD-L1 test has been done on the tumour sample and whether immunotherapy before and after surgery is right for you [1]. Not all doctors agree on how big its benefit is [3, 4]; make the decision together with your care team (head and neck cancers).
What was reported?
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For years the standard treatment of resectable locally advanced head and neck squamous cell carcinoma (HNSCC) has been surgery followed by radiotherapy with or without cisplatin, and the place of adding immunotherapy to this pathway was unclear [1].
In the open-label phase 3 KEYNOTE-689 trial, participants were randomised to either 2 cycles of pembrolizumab before surgery and 15 cycles after surgery together with standard treatment, or standard treatment alone [1]. The primary endpoint was event-free survival, tested in turn in the CPS 10 or higher group, the CPS 1 or higher group and all patients [1].
With a median follow-up of 38.3 months, 3-year event-free survival was 59.8% vs 45.9% in the CPS 10 or higher group, 58.2% vs 44.9% in the CPS 1 or higher group and 57.6% vs 46.4% in all patients [1]. A comparative review showed that KEYNOTE-689 particularly reduced distant recurrence [2].
If you have squamous cell head and neck cancer (such as cancer of the mouth or voice box) and are going to have surgery, there is now an immunotherapy option that starts before the operation, continues after it together with radiotherapy and then on its own, and lowers the chance of the cancer coming back [1]. This treatment did not delay surgery, and its severe side effects were about the same as with standard treatment [1]. To find out whether it is right for you, a PD-L1 test (CPS score) on the tumour sample is needed; talk with your care team.
Trial details and regimen (for physicians)
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- Treatment-related grade 3 or higher adverse events 44.6% vs 42.9%; treatment-related deaths 1.1% vs 0.3%; grade 3 or higher immune-related adverse events 10.0% [1].
- Overall survival data are still immature [2]; some experts in JCO have questioned the clinical benefit of this approach [3], and the German Society for Radiation Oncology (DEGRO) has published a statement on combining it with adjuvant radiotherapy [4].
- The NIVOPOSTOP trial (nivolumab with postoperative chemoradiotherapy in high-risk patients) also improved disease-free survival (hazard ratio 0.76); the choice between the two approaches depends on the risk of recurrence, PD-L1 expression and the multidisciplinary team's decision [2].
KEYNOTE-689 regimen (FDA label)
Pembrolizumab before and after surgery
Resectable locally advanced HNSCC (stage III to IVA) with PD-L1 CPS 1 or higherCycle length: Every 3 weeks
Resectable locally advanced HNSCC (stage III to IVA) with PD-L1 CPS 1 or higher
| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Before surgery | |||
| Pembrolizumab | 200 mg | IV infusion over 30 minutes | Every 3 weeks, 2 cycles (6 weeks) |
| Within 6 weeks after surgery, with radiotherapy | |||
| Pembrolizumab | 200 mg | IV, before cisplatin on the same day | Every 3 weeks, 3 cycles |
| Only for high-risk pathology | |||
| Cisplatin concurrent with radiotherapy | 100 mg/m² | IV | Every 3 weeks, 3 cycles |
| Maintenance | |||
| Pembrolizumab | 200 mg | IV | Every 3 weeks, up to 12 cycles |
High-risk pathology: positive margin of less than 1 mm or extranodal extension. The FDA label also allows a dose of 400 mg every 6 weeks. Before starting: PD-L1 (CPS) testing, liver enzymes, creatinine and thyroid function. Dose reduction is not recommended; immune-related adverse events are managed by withholding or discontinuing and corticosteroids [5].
Doses follow the trial protocol, guideline or official drug label (source given in the notes of each regimen). Before prescribing, check blood counts, renal and hepatic function, drug interactions and the patient’s condition, and adjust the dose according to the drug label.
Limitations and next steps
- Approval: on 12 June 2025 the FDA approved pembrolizumab for adults with resectable locally advanced HNSCC with PD-L1 CPS 1 or higher, as neoadjuvant treatment, continued as adjuvant treatment with radiotherapy ± cisplatin and then as a single agent (FDA announcement).
- The study was open-label and the results reported are from the first interim analysis [1].
- The benefit in the whole population was smaller than in the PD-L1-positive groups; tumours with CPS below 1 are not covered by the FDA approval [1].
The main study
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Key study
1 itemNeoadjuvant and Adjuvant Pembrolizumab in Locally Advanced Head and Neck Cancer
References
5 referencesShow all references, 4 with a study cardClose the reference list
Numbers in the text, such as [1], refer to these sources. Sources with a “Study card” button are summarised in the site’s evidence library.
- 1
- 2
- 3Notably Off Key: Questioning the Clinical Benefit of Perioperative Immunotherapy for Resectable Head and Neck Squamous Cell Carcinoma After KEYNOTE-689
- 4DEGRO statement on the KEYNOTE-689 trial: Perioperative immunotherapy in combination with adjuvant (chemo-)radiotherapy for resectable locally advanced head and neck cancers
- 5KEYTRUDA (pembrolizumab) injection, for intravenous use: Prescribing Information
This page is based on reputable scientific sources and was last updated on 28 October 2026. The content of this website is for educational and informational purposes only and does not replace consultation, diagnosis or treatment by a specialist physician. Consult your treating physician about any treatment decision.
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