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KEYNOTE-412

Pembrolizumab plus concurrent chemoradiotherapy versus placebo plus concurrent chemoradiotherapy in locally advanced squamous cell carcinoma of the head and neck

Phase 3N = 804NCT03040999

Population
Newly diagnosed, high-risk, unresected locally advanced head and neck squamous cell carcinoma
Design
Randomised, double-blind phase 3 trial at 130 centres. 804 participants with newly diagnosed, high-risk, unresected locally advanced HNSCC were randomly assigned 1:1 to pembrolizumab 200 mg or placebo every 3 weeks for up to 17 doses (one before chemoradiotherapy, two during, 14 as maintenance) with cisplatin (100 mg per square metre every 3 weeks, two or three doses) and accelerated or standard fractionation radiotherapy (70 Gy in 35 fractions). The primary endpoint was event-free survival in all randomly assigned participants.
Primary endpoint
EFS
Arms
  • Pembrolizumab plus chemoradiotherapy (experimental, n = 402): Pembrolizumab 200 mg every 3 weeks with cisplatin and radiotherapy, then maintenance
  • Placebo plus chemoradiotherapy (control, n = 402): Placebo with cisplatin and radiotherapy, then maintenance placebo
People
Machiels JP, KEYNOTE-412 Investigators
EFSHR 0.83 (95% CI 0.68–1.03)
Show the numbers
Results reported for KEYNOTE-412
EndpointAnalysisPembrolizumab plus chemoradiotherapyPlacebo plus chemoradiotherapyEffect
EFSAll randomly assigned participants (N = 804)primarymedian follow-up 47.7 monthsMachiels 2024——HR 0.83 (95% CI 0.68–1.03)P=0.043Described in the abstract as not significantly improved: the p value of 0.043 did not meet the prespecified significance threshold of p <= 0.024. Median EFS was not reached with pembrolizumab (95% CI 44.7 months to not reached) and was 46.6 months with placebo (95% CI 27.5 months to not reached).
Results reported for KEYNOTE-412
EndpointAnalysisPembrolizumab plus chemoradiotherapyPlacebo plus chemoradiotherapyEffect
EFSAll randomly assigned participants (N = 804)primarymedian follow-up 47.7 monthsMachiels 2024——HR 0.83 (95% CI 0.68–1.03)P=0.043Described in the abstract as not significantly improved: the p value of 0.043 did not meet the prespecified significance threshold of p <= 0.024. Median EFS was not reached with pembrolizumab (95% CI 44.7 months to not reached) and was 46.6 months with placebo (95% CI 27.5 months to not reached).
Hazard ratio (95% CI) by endpoint. Values below 1 favour the experimental arm.
EFS0.512◀ experimentalcontrol ▶
Data table
EndpointHR95% CI
EFS0.830.68–1.03
Primary publication: Machiels JP, Tao Y, Licitra L, Burtness B, Tahara M, Rischin D, et al. Pembrolizumab plus concurrent chemoradiotherapy versus placebo plus concurrent chemoradiotherapy in patients with locally advanced squamous cell carcinoma of the head and neck (KEYNOTE-412): a randomised, double-blind, phase 3 trial. Lancet Oncol. 2024;25(5):572-587. PubMedDOI

Appears in

Sources

  1. Machiels JP, Tao Y, Licitra L, Burtness B, Tahara M, Rischin D, et al. Pembrolizumab plus concurrent chemoradiotherapy versus placebo plus concurrent chemoradiotherapy in patients with locally advanced squamous cell carcinoma of the head and neck (KEYNOTE-412): a randomised, double-blind, phase 3 trial. Lancet Oncol. 2024;25(5):572-587.

    PubMedDOI