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Bending the Curve Trial by Trial
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METRIC

GSK1120212 vs Chemotherapy in Advanced or Metastatic BRAF V600E/K Mutation-positive Melanoma

Phase 3N = 322NCT01245062

Population
Metastatic melanoma with a BRAF V600E or V600K mutation
Design
Open-label randomised (2:1) phase 3 trial of trametinib 2 mg orally once daily versus intravenous dacarbazine 1,000 mg per square metre or paclitaxel 175 mg per square metre every 3 weeks; patients in the chemotherapy group with progression were permitted to cross over to trametinib. Primary end point progression-free survival; overall survival secondary.
Primary endpoint
PFS
Arms
  • Trametinib (experimental): Trametinib 2 mg orally once daily
  • Chemotherapy (control): Dacarbazine 1,000 mg per square metre or paclitaxel 175 mg per square metre intravenously every 3 weeks
People
Flaherty KT, senior author Schadendorf D
PFSHR 0.45 (95% CI 0.33–0.63)Δ median PFS+3.3 monthsOSHR 0.54 (95% CI 0.32–0.92)Δ 6-month OS+14 points
Show the numbers
Results reported for METRIC
EndpointAnalysisTrametinibChemotherapyEffect
PFSRandomised population as described in the abstract (analysis population not stated there)primaryFlaherty 2012median 4.8 monthsmedian 1.5 monthsHR 0.45 (95% CI 0.33–0.63)P<0.001
OSRandomised population as described in the abstract (analysis population not stated there)primaryFlaherty 201281% at 6 mo67% at 6 moHR 0.54 (95% CI 0.32–0.92)P=0.01Overall survival at 6 months despite crossover from chemotherapy to trametinib; overall survival was a secondary end point. The abstract does not say whether this was an interim analysis.
Results reported for METRIC
EndpointAnalysisTrametinibChemotherapyEffect
PFSRandomised population as described in the abstract (analysis population not stated there)primaryFlaherty 2012median 4.8 monthsmedian 1.5 monthsHR 0.45 (95% CI 0.33–0.63)P<0.001
OSRandomised population as described in the abstract (analysis population not stated there)primaryFlaherty 201281% at 6 mo67% at 6 moHR 0.54 (95% CI 0.32–0.92)P=0.01Overall survival at 6 months despite crossover from chemotherapy to trametinib; overall survival was a secondary end point. The abstract does not say whether this was an interim analysis.
Hazard ratio (95% CI) by endpoint. Values below 1 favour the experimental arm.
PFSOS0.512◀ experimentalcontrol ▶
Data table
EndpointHR95% CI
PFS0.450.33–0.63
OS0.540.32–0.92
Illustrative — modelled from reported values, not trial data. PFS, primary.
0%25%50%75%100%024681012Months (modelled)
  • Trametinib (experimental)
  • Chemotherapy (control)

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

Data table (modelled values)
MonthsTrametinibChemotherapy
0100.0%100.0%
364.8%25.0%
642.0%6.3%
927.3%1.6%
1217.7%0.4%
Primary publication: Flaherty KT, Robert C, Hersey P, Nathan P, Garbe C, Milhem M, et al. Improved survival with MEK inhibition in BRAF-mutated melanoma. N Engl J Med. 2012;367(2):107-14. PubMedDOI

Appears in

Sources

  1. Flaherty KT, Robert C, Hersey P, Nathan P, Garbe C, Milhem M, et al. Improved survival with MEK inhibition in BRAF-mutated melanoma. N Engl J Med. 2012;367(2):107-14.

    PubMedDOI