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Bending the Curve Trial by Trial
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ADMIRAL

Gilteritinib or chemotherapy for relapsed or refractory FLT3-mutated AML

Phase 3N = 371NCT02421939

Population
Adults with relapsed or refractory FLT3-mutated AML
Design
Phase 3 trial randomizing adults 2:1 to gilteritinib 120 mg per day or salvage chemotherapy. Two primary end points: overall survival and the percentage of patients with complete remission with full or partial hematologic recovery. Secondary end points included event-free survival and the percentage with complete remission.
Primary endpoint
OS, CR+CRh
Arms
  • Gilteritinib (experimental, n = 247): Gilteritinib 120 mg orally per day
  • Salvage chemotherapy (control, n = 124): Salvage chemotherapy (regimens not specified in the abstract)
People
Perl AE
OSHR 0.64 (95% CI 0.49–0.83)Δ median OS+3.7 monthsΔ CR+CRh+18.7 pointsΔ CR+10.6 pointsEFSHR 0.79 (95% CI 0.58–1.09)Δ median EFS+2.1 months
Show the numbers
Results reported for ADMIRAL
EndpointAnalysisGilteritinibSalvage chemotherapyEffect
OSRandomized patients (371 eligible); the abstract does not use the term ITTprimaryPerl 2019median 9.3 monthsmedian 5.6 monthsHR 0.64 (95% CI 0.49–0.83)P<0.001
CR+CRhRandomized patients (371 eligible); the abstract does not use the term ITTComplete remission with full or partial hematologic recoveryprimaryPerl 201934%15.3%Risk difference 18.6 percentage points (95% CI 9.8 to 27.4).
CRRandomized patients (371 eligible); the abstract does not use the term ITTprimaryPerl 201921.1%10.5%Risk difference 10.6 percentage points (95% CI 2.8 to 18.4).
EFSRandomized patients (371 eligible); the abstract does not use the term ITTprimaryPerl 2019median 2.8 monthsmedian 0.7 monthsHR 0.79 (95% CI 0.58–1.09)Secondary end point; the abstract gives no P value, and the confidence interval for the hazard ratio includes 1.0.
Results reported for ADMIRAL
EndpointAnalysisGilteritinibSalvage chemotherapyEffect
OSRandomized patients (371 eligible); the abstract does not use the term ITTprimaryPerl 2019median 9.3 monthsmedian 5.6 monthsHR 0.64 (95% CI 0.49–0.83)P<0.001
CR+CRhRandomized patients (371 eligible); the abstract does not use the term ITTComplete remission with full or partial hematologic recoveryprimaryPerl 201934%15.3%Risk difference 18.6 percentage points (95% CI 9.8 to 27.4).
CRRandomized patients (371 eligible); the abstract does not use the term ITTprimaryPerl 201921.1%10.5%Risk difference 10.6 percentage points (95% CI 2.8 to 18.4).
EFSRandomized patients (371 eligible); the abstract does not use the term ITTprimaryPerl 2019median 2.8 monthsmedian 0.7 monthsHR 0.79 (95% CI 0.58–1.09)Secondary end point; the abstract gives no P value, and the confidence interval for the hazard ratio includes 1.0.
Hazard ratio (95% CI) by endpoint. Values below 1 favour the experimental arm.
OSEFS0.512◀ experimentalcontrol ▶
Data table
EndpointHR95% CI
OS0.640.49–0.83
EFS0.790.58–1.09
Illustrative — modelled from reported values, not trial data. OS, primary.
0%25%50%75%100%05101520Months (modelled)
  • Gilteritinib (experimental)
  • Salvage chemotherapy (control)

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

Data table (modelled values)
MonthsGilteritinibSalvage chemotherapy
0100.0%100.0%
663.9%47.6%
1240.9%22.6%
1728.2%12.2%
2318.0%5.8%
Illustrative — modelled from reported values, not trial data. EFS, primary.
0%25%50%75%100%01234567Months (modelled)
  • Gilteritinib (experimental)
  • Salvage chemotherapy (control)

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

Data table (modelled values)
MonthsGilteritinibSalvage chemotherapy
0100.0%100.0%
261.0%13.8%
437.1%1.9%
529.0%0.7%
717.7%0.1%
Primary publication: Perl AE, Martinelli G, Cortes JE, Neubauer A, Berman E, Paolini S, et al. Gilteritinib or Chemotherapy for Relapsed or Refractory FLT3-Mutated AML. N Engl J Med. 2019;381(18):1728-1740. PubMedDOI

Appears in

Sources

  1. Perl AE, Martinelli G, Cortes JE, Neubauer A, Berman E, Paolini S, et al. Gilteritinib or Chemotherapy for Relapsed or Refractory FLT3-Mutated AML. N Engl J Med. 2019;381(18):1728-1740.

    PubMedDOI