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Bending the Curve Trial by Trial
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COMBI-v

Dabrafenib Plus Trametinib vs Vemurafenib Alone in Unresectable or Metastatic BRAF V600E/K Cutaneous Melanoma

Phase 3N = 704NCT01597908

Population
Previously untreated unresectable or metastatic melanoma with a BRAF V600E or V600K mutation
Design
Open-label randomised phase 3 trial of dabrafenib 150 mg twice daily plus trametinib 2 mg once daily versus vemurafenib 960 mg twice daily as first-line therapy. Primary end point overall survival; the first report is the preplanned interim analysis after 77% of the expected events, at which the study was stopped for efficacy in July 2014.
Primary endpoint
OS
Arms
  • Dabrafenib plus trametinib (experimental, n = 352): Dabrafenib 150 mg twice daily plus trametinib 2 mg once daily
  • Vemurafenib (control): Vemurafenib 960 mg twice daily
People
Robert C, senior author Schadendorf D
OSHR 0.69 (95% CI 0.53–0.89)Δ 12-month OS+7 pointsPFSHR 0.56 (95% CI 0.46–0.69)Δ median PFS+4.1 monthsΔ ORR+13 points
Show the numbers
Results reported for COMBI-v
EndpointAnalysisDabrafenib plus trametinibVemurafenibEffect
OSRandomised population as described in the abstract (analysis population not stated there)interimRobert 201572% at 12 mo (67–77%)65% at 12 mo (59–70%)HR 0.69 (95% CI 0.53–0.89)P=0.005Preplanned interim analysis after 77% of the total number of expected events; the prespecified interim stopping boundary was crossed and the study was stopped for efficacy in July 2014.
PFSRandomised population as described in the abstract (analysis population not stated there)interimRobert 2015median 11.4 monthsmedian 7.3 monthsHR 0.56 (95% CI 0.46–0.69)P<0.001
ORRRandomised population as described in the abstract (analysis population not stated there)interimRobert 201564%51%P<0.001
Results reported for COMBI-v
EndpointAnalysisDabrafenib plus trametinibVemurafenibEffect
OSRandomised population as described in the abstract (analysis population not stated there)interimRobert 201572% at 12 mo (67–77%)65% at 12 mo (59–70%)HR 0.69 (95% CI 0.53–0.89)P=0.005Preplanned interim analysis after 77% of the total number of expected events; the prespecified interim stopping boundary was crossed and the study was stopped for efficacy in July 2014.
PFSRandomised population as described in the abstract (analysis population not stated there)interimRobert 2015median 11.4 monthsmedian 7.3 monthsHR 0.56 (95% CI 0.46–0.69)P<0.001
ORRRandomised population as described in the abstract (analysis population not stated there)interimRobert 201564%51%P<0.001
Hazard ratio (95% CI) by endpoint. Values below 1 favour the experimental arm.
OSPFS0.512◀ experimentalcontrol ▶
Data table
EndpointHR95% CI
OS0.690.53–0.89
PFS0.560.46–0.69
Illustrative — modelled from reported values, not trial data. PFS, interim.
0%25%50%75%100%0510152025Months (modelled)
  • Dabrafenib plus trametinib (experimental)
  • Vemurafenib (control)

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

Data table (modelled values)
MonthsDabrafenib plus trametinibVemurafenib
0100.0%100.0%
765.3%51.4%
1442.7%26.5%
2127.9%13.6%
2917.1%6.4%
Primary publication: Robert C, Karaszewska B, Schachter J, Rutkowski P, Mackiewicz A, Stroiakovski D, et al. Improved overall survival in melanoma with combined dabrafenib and trametinib. N Engl J Med. 2015;372(1):30-9. PubMedDOI

Appears in

Sources

  1. Robert C, Karaszewska B, Schachter J, Rutkowski P, Mackiewicz A, Stroiakovski D, et al. Improved overall survival in melanoma with combined dabrafenib and trametinib. N Engl J Med. 2015;372(1):30-9.

    PubMedDOI