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Bending the Curve Trial by Trial
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EXAMINER

A Randomized, Double-blind Study To Evaluate the Efficacy and Safety of Cabozantinib (XL184) at 60 mg/Day Compared to a 140 mg/Day in Progressive, Metastatic Medullary Thyroid Cancer Patients

N = 247NCT01896479

Population
Progressive, metastatic medullary thyroid cancer
Design
Phase 4, randomised (1:1), double-blind non-inferiority trial of cabozantinib 60 mg/day tablets versus 140 mg/day capsules. Primary endpoint progression-free survival by blinded independent radiology committee (RECIST 1.1); non-inferiority concluded if the upper 95% CI of the PFS hazard ratio was below the margin of 1.58. Secondary endpoint objective response rate; data cutoff 15 July 2020.
Primary endpoint
PFS
Arms
  • Cabozantinib capsules 140 mg/day (control, n = 124): Cabozantinib capsules 140 mg per day
  • Cabozantinib tablet 60 mg/day (experimental, n = 123): Cabozantinib tablet 60 mg per day
People
Capdevila J, senior author Jarzab B
PFSHR 1.24 (95% CI 0.9–1.7)Δ median PFS−2.9 monthsΔ ORR0 points
Show the numbers
Results reported for EXAMINER
EndpointAnalysisCabozantinib tablet 60 mg/dayCabozantinib capsules 140 mg/dayEffect
PFSRandomised patients (247)primaryCapdevila 2022median 11 monthsmedian 13.9 monthsHR 1.24 (95% CI 0.9–1.7)P=0.19Non-inferiority of the 60 mg/day tablet was not met. Grade 3/4 adverse events 63% (60 mg/day) versus 72% (140 mg/day); dose reductions 69% versus 81%; treatment discontinuations due to adverse events 23% versus 36%.
ORRRandomised patients (247)primaryCapdevila 202233%33%The abstract reports an objective response rate of 33% in both arms.
Results reported for EXAMINER
EndpointAnalysisCabozantinib tablet 60 mg/dayCabozantinib capsules 140 mg/dayEffect
PFSRandomised patients (247)primaryCapdevila 2022median 11 monthsmedian 13.9 monthsHR 1.24 (95% CI 0.9–1.7)P=0.19Non-inferiority of the 60 mg/day tablet was not met. Grade 3/4 adverse events 63% (60 mg/day) versus 72% (140 mg/day); dose reductions 69% versus 81%; treatment discontinuations due to adverse events 23% versus 36%.
ORRRandomised patients (247)primaryCapdevila 202233%33%The abstract reports an objective response rate of 33% in both arms.
Hazard ratio (95% CI) by endpoint. Values below 1 favour the experimental arm.
PFS0.512◀ experimentalcontrol ▶
Data table
EndpointHR95% CI
PFS1.240.9–1.7
Illustrative — modelled from reported values, not trial data. PFS, primary.
0%25%50%75%100%051015202530Months (modelled)
  • Cabozantinib tablet 60 mg/day (experimental)
  • Cabozantinib capsules 140 mg/day (control)

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

Data table (modelled values)
MonthsCabozantinib tablet 60 mg/dayCabozantinib capsules 140 mg/day
0100.0%100.0%
956.7%63.8%
1734.3%42.8%
2619.4%27.3%
3511.0%17.5%
Primary publication: Capdevila J, Klochikhin A, Leboulleux S, Isaev P, Badiu C, Robinson B, et al. A Randomized, Double-Blind Noninferiority Study to Evaluate the Efficacy of the Cabozantinib Tablet at 60 mg Per Day Compared with the Cabozantinib Capsule at 140 mg Per Day in Patients with Progressive, Metastatic Medullary Thyroid Cancer. Thyroid. 2022;32(5):515-524. PubMedDOI

Appears in

Sources

  1. Capdevila J, Klochikhin A, Leboulleux S, Isaev P, Badiu C, Robinson B, et al. A Randomized, Double-Blind Noninferiority Study to Evaluate the Efficacy of the Cabozantinib Tablet at 60 mg Per Day Compared with the Cabozantinib Capsule at 140 mg Per Day in Patients with Progressive, Metastatic Medullary Thyroid Cancer. Thyroid. 2022;32(5):515-524.

    PubMedDOI