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Bending the Curve Trial by Trial
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KEYNOTE-040

Needs review

Pembrolizumab versus methotrexate, docetaxel, or cetuximab for recurrent or metastatic head-and-neck squamous cell carcinoma

Phase 3N = 495NCT02252042

Population
Head-and-neck squamous cell carcinoma progressing during or after platinum-containing therapy
Design
Randomised, open-label phase 3 study at 97 medical centres in 20 countries. 495 patients (247 and 248 per arm) with head-and-neck squamous cell carcinoma that progressed during or after platinum-containing treatment for recurrent or metastatic disease (or both), or recurred or progressed within 3-6 months of platinum-containing multimodal therapy for locally advanced disease, were randomised 1:1 to pembrolizumab 200 mg every 3 weeks or investigator's choice of standard doses of methotrexate, docetaxel or cetuximab. The primary endpoint was overall survival in the intention-to-treat population.
Primary endpoint
OS
Arms
  • Pembrolizumab (experimental, n = 247): Pembrolizumab 200 mg intravenously every 3 weeks
  • Investigator's choice (control, n = 248): Methotrexate, docetaxel or cetuximab at standard doses
People
Cohen EEW, KEYNOTE-040
OSHR 0.80 (95% CI 0.65–0.98)Δ median OS+1.5 months
Show the numbers
Results reported for KEYNOTE-040
EndpointAnalysisPembrolizumabInvestigator's choiceEffect
OSprimaryCohen 2019median 8.4 months (6.4–9.4)median 6.9 months (5.9–8.0)HR 0.80 (95% CI 0.65–0.98)P=0.0161The abstract describes the p value as nominal. 181 of 247 (73%) and 207 of 248 (83%) patients had died as of 15 May 2017.
Results reported for KEYNOTE-040
EndpointAnalysisPembrolizumabInvestigator's choiceEffect
OSprimaryCohen 2019median 8.4 months (6.4–9.4)median 6.9 months (5.9–8.0)HR 0.80 (95% CI 0.65–0.98)P=0.0161The abstract describes the p value as nominal. 181 of 247 (73%) and 207 of 248 (83%) patients had died as of 15 May 2017.
Hazard ratio (95% CI) by endpoint. Values below 1 favour the experimental arm.
OS0.512◀ experimentalcontrol ▶
Data table
EndpointHR95% CI
OS0.80.65–0.98
Illustrative — modelled from reported values, not trial data. OS, primary.
0%25%50%75%100%05101520Months (modelled)
  • Pembrolizumab (experimental)
  • Investigator's choice (control)

Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.

Data table (modelled values)
MonthsPembrolizumabInvestigator's choice
0100.0%100.0%
566.2%60.5%
1140.3%33.1%
1626.7%20.0%
2117.7%12.1%
Primary publication: Cohen EEW, Soulières D, Le Tourneau C, Dinis J, Licitra L, Ahn MJ, et al. Pembrolizumab versus methotrexate, docetaxel, or cetuximab for recurrent or metastatic head-and-neck squamous cell carcinoma (KEYNOTE-040): a randomised, open-label, phase 3 study. Lancet. 2019;393(10167):156-167. PubMedDOI

Appears in

Sources

  1. Cohen EEW, Soulières D, Le Tourneau C, Dinis J, Licitra L, Ahn MJ, et al. Pembrolizumab versus methotrexate, docetaxel, or cetuximab for recurrent or metastatic head-and-neck squamous cell carcinoma (KEYNOTE-040): a randomised, open-label, phase 3 study. Lancet. 2019;393(10167):156-167.

    PubMedDOI