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Bending the Curve Trial by Trial
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A Study Comparing GSK2118436 to Dacarbazine (DTIC) in Previously Untreated Subjects With BRAF Mutation Positive Advanced (Stage III) or Metastatic (Stage IV) Melanoma

Phase 3N = 250NCT01227889

Population
Previously untreated stage IV or unresectable stage III melanoma with a BRAF V600E mutation
Design
Open-label randomised (3:1) phase 3 trial of dabrafenib 150 mg twice daily orally versus dacarbazine 1,000 mg per square metre intravenously every 3 weeks, stratified by AJCC stage. Primary end point investigator-assessed progression-free survival, analysed by intention to treat; data cutoff 19 December 2011. The registry record lists 251 enrolled; the paper randomised 250.
Primary endpoint
PFS
Arms
  • Dabrafenib (experimental, n = 187): Dabrafenib 150 mg orally twice daily
  • Dacarbazine (control, n = 63): Dacarbazine 1,000 mg per square metre intravenously every 3 weeks
People
Hauschild A, senior author Chapman PB
PFSHR 0.30 (95% CI 0.18–0.51)Δ median PFS+2.4 months
Show the numbers
Results reported for A Study Comparing GSK2118436 to Dacarbazine (DTIC) in Previously Untreated Subjects With BRAF Mutation Positive Advanced (Stage III) or Metastatic (Stage IV) Melanoma
EndpointAnalysisDabrafenibDacarbazineEffect
PFSprimaryHauschild 2012median 5.1 monthsmedian 2.7 monthsHR 0.30 (95% CI 0.18–0.51)P<0.0001Investigator-assessed progression-free survival.
Results reported for A Study Comparing GSK2118436 to Dacarbazine (DTIC) in Previously Untreated Subjects With BRAF Mutation Positive Advanced (Stage III) or Metastatic (Stage IV) Melanoma
EndpointAnalysisDabrafenibDacarbazineEffect
PFSprimaryHauschild 2012median 5.1 monthsmedian 2.7 monthsHR 0.30 (95% CI 0.18–0.51)P<0.0001Investigator-assessed progression-free survival.
Hazard ratio (95% CI) by endpoint. Values below 1 favour the experimental arm.
PFS0.512◀ experimentalcontrol ▶
Data table
EndpointHR95% CI
PFS0.30.18–0.51
Illustrative — modelled from reported values, not trial data. PFS, primary.
0%25%50%75%100%024681012Months (modelled)
  • Dabrafenib (experimental)
  • Dacarbazine (control)

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

Data table (modelled values)
MonthsDabrafenibDacarbazine
0100.0%100.0%
366.5%46.3%
644.2%21.4%
1025.7%7.7%
1317.1%3.6%
Primary publication: Hauschild A, Grob JJ, Demidov LV, Jouary T, Gutzmer R, Millward M, et al. Dabrafenib in BRAF-mutated metastatic melanoma: a multicentre, open-label, phase 3 randomised controlled trial. Lancet. 2012;380(9839):358-65. PubMedDOI

Appears in

Sources

  1. Hauschild A, Grob JJ, Demidov LV, Jouary T, Gutzmer R, Millward M, et al. Dabrafenib in BRAF-mutated metastatic melanoma: a multicentre, open-label, phase 3 randomised controlled trial. Lancet. 2012;380(9839):358-65.

    PubMedDOI