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KEYNOTE-689

Neoadjuvant and adjuvant pembrolizumab plus standard care versus standard care alone in resectable locally advanced head and neck squamous-cell carcinoma

Phase 3N = 714NCT03765918

Population
Resectable locally advanced head and neck squamous-cell carcinoma (234 of 363 and 231 of 351 participants with CPS 10 or more; 347 and 335 with CPS 1 or more)
Design
Open-label phase 3 trial. Participants with locally advanced HNSCC were randomly assigned 1:1 to 2 cycles of neoadjuvant pembrolizumab and 15 cycles of adjuvant pembrolizumab (both 200 mg every 3 weeks) in addition to standard care, or to standard care alone (surgery and adjuvant radiotherapy with or without concomitant cisplatin). The primary end point was event-free survival, assessed sequentially in the CPS 10 or more, CPS 1 or more and total populations.
Primary endpoint
EFS
Arms
  • Pembrolizumab plus standard care (experimental, n = 363): Neoadjuvant pembrolizumab (2 cycles), then surgery and adjuvant radiotherapy with or without cisplatin, with adjuvant pembrolizumab (15 cycles in total)
  • Standard care alone (control, n = 351): Surgery and adjuvant radiotherapy with or without concomitant cisplatin
People
Uppaluri R, KEYNOTE-689 Investigators
EFSHR 0.66 (95% CI 0.49–0.88)Δ 36-month EFS+13.9 pointsEFSHR 0.70 (95% CI 0.55–0.89)Δ 36-month EFS+13.3 pointsEFSHR 0.73 (95% CI 0.58–0.92)Δ 36-month EFS+11.2 points
Show the numbers
Results reported for KEYNOTE-689
EndpointAnalysisPembrolizumab plus standard careStandard care aloneEffect
EFSPD-L1 CPS 10 or more (234 pembrolizumab, 231 control)interimmedian follow-up 38.3 monthsUppaluri 202559.8% at 3 y45.9% at 3 yHR 0.66 (95% CI 0.49–0.88)P=0.004First interim analysis; the hazard ratio is for progression, recurrence or death and the P value is two-sided.
EFSPD-L1 CPS 1 or more (347 pembrolizumab, 335 control)interimmedian follow-up 38.3 monthsUppaluri 202558.2% at 3 y44.9% at 3 yHR 0.70 (95% CI 0.55–0.89)P=0.003First interim analysis; the hazard ratio is for progression, recurrence or death and the P value is two-sided.
EFSTotal population (363 pembrolizumab, 351 control)interimmedian follow-up 38.3 monthsUppaluri 202557.6% at 3 y46.4% at 3 yHR 0.73 (95% CI 0.58–0.92)P=0.008First interim analysis; the hazard ratio is for progression, recurrence or death and the P value is two-sided.
Results reported for KEYNOTE-689
EndpointAnalysisPembrolizumab plus standard careStandard care aloneEffect
EFSPD-L1 CPS 10 or more (234 pembrolizumab, 231 control)interimmedian follow-up 38.3 monthsUppaluri 202559.8% at 3 y45.9% at 3 yHR 0.66 (95% CI 0.49–0.88)P=0.004First interim analysis; the hazard ratio is for progression, recurrence or death and the P value is two-sided.
EFSPD-L1 CPS 1 or more (347 pembrolizumab, 335 control)interimmedian follow-up 38.3 monthsUppaluri 202558.2% at 3 y44.9% at 3 yHR 0.70 (95% CI 0.55–0.89)P=0.003First interim analysis; the hazard ratio is for progression, recurrence or death and the P value is two-sided.
EFSTotal population (363 pembrolizumab, 351 control)interimmedian follow-up 38.3 monthsUppaluri 202557.6% at 3 y46.4% at 3 yHR 0.73 (95% CI 0.58–0.92)P=0.008First interim analysis; the hazard ratio is for progression, recurrence or death and the P value is two-sided.
Hazard ratio (95% CI) by endpoint. Values below 1 favour the experimental arm.
EFSEFSEFS0.512◀ experimentalcontrol ▶
Data table
EndpointHR95% CI
EFS0.660.49–0.88
EFS0.70.55–0.89
EFS0.730.58–0.92
Primary publication: Uppaluri R, Haddad RI, Tao Y, Le Tourneau C, Lee NY, Westra W, et al. Neoadjuvant and Adjuvant Pembrolizumab in Locally Advanced Head and Neck Cancer. N Engl J Med. 2025;393(1):37-50. PubMedDOI

Appears in

Sources

  1. Uppaluri R, Haddad RI, Tao Y, Le Tourneau C, Lee NY, Westra W, et al. Neoadjuvant and Adjuvant Pembrolizumab in Locally Advanced Head and Neck Cancer. N Engl J Med. 2025;393(1):37-50.

    PubMedDOI