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Bending the Curve Trial by Trial
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BRIM-3

A Study of Vemurafenib (RO5185426) in Comparison With Dacarbazine in Previously Untreated Patients With Metastatic Melanoma (BRIM 3)

Phase 3N = 675NCT01006980

Population
Previously untreated metastatic melanoma with the BRAF V600E mutation
Design
Open-label randomised (1:1) phase 3 trial of vemurafenib 960 mg orally twice daily versus dacarbazine 1,000 mg per square metre intravenously every 3 weeks. Overall survival and progression-free survival were co-primary end points; final analysis was planned after 196 deaths and an interim analysis after 98 deaths. After review of the interim analysis by an independent data and safety monitoring board, crossover from dacarbazine to vemurafenib was recommended.
Primary endpoint
OS, PFS
Arms
  • Vemurafenib (experimental, n = 337): Vemurafenib 960 mg orally twice daily
  • Dacarbazine (control, n = 338): Dacarbazine 1,000 mg per square metre intravenously every 3 weeks
People
Chapman PB, senior author McArthur GA
OSHR 0.37 (95% CI 0.26–0.55)Δ 6-month OS+20 pointsPFSHR 0.26 (95% CI 0.20–0.33)Δ median PFS+3.7 monthsΔ ORR+43 points
Show the numbers
Results reported for BRIM-3
EndpointAnalysisVemurafenibDacarbazineEffect
OSIntention-to-treat population; 672 patients evaluable for overall survival (full text)interimChapman 201184% at 6 mo (78–89%)64% at 6 mo (56–73%)HR 0.37 (95% CI 0.26–0.55)P<0.001Interim analysis for overall survival (after 98 deaths planned; 118 patients had died at the clinical cutoff of 30 December 2010 per the full text). The abstract states a 63% relative reduction in the risk of death; the hazard ratio and its interval are from the full text.
PFSIntention-to-treat population; 549 patients evaluable for progression-free survival (full text)finalChapman 2011median 5.3 monthsmedian 1.6 monthsHR 0.26 (95% CI 0.20–0.33)P<0.001Final analysis for progression-free survival.
ORRPatients evaluable for response (219 and 220)interimChapman 201148% (42–55%)5% (3–9%)P<0.001Confirmed response rates; 106 of 219 versus 12 of 220 patients.
Results reported for BRIM-3
EndpointAnalysisVemurafenibDacarbazineEffect
OSIntention-to-treat population; 672 patients evaluable for overall survival (full text)interimChapman 201184% at 6 mo (78–89%)64% at 6 mo (56–73%)HR 0.37 (95% CI 0.26–0.55)P<0.001Interim analysis for overall survival (after 98 deaths planned; 118 patients had died at the clinical cutoff of 30 December 2010 per the full text). The abstract states a 63% relative reduction in the risk of death; the hazard ratio and its interval are from the full text.
PFSIntention-to-treat population; 549 patients evaluable for progression-free survival (full text)finalChapman 2011median 5.3 monthsmedian 1.6 monthsHR 0.26 (95% CI 0.20–0.33)P<0.001Final analysis for progression-free survival.
ORRPatients evaluable for response (219 and 220)interimChapman 201148% (42–55%)5% (3–9%)P<0.001Confirmed response rates; 106 of 219 versus 12 of 220 patients.
Hazard ratio (95% CI) by endpoint. Values below 1 favour the experimental arm.
OSPFS0.512◀ experimentalcontrol ▶
Data table
EndpointHR95% CI
OS0.370.26–0.55
PFS0.260.2–0.33
Illustrative — modelled from reported values, not trial data. PFS, final.
0%25%50%75%100%024681012Months (modelled)
  • Vemurafenib (experimental)
  • Dacarbazine (control)

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

Data table (modelled values)
MonthsVemurafenibDacarbazine
0100.0%100.0%
367.5%27.3%
740.0%4.8%
1027.0%1.3%
1318.3%0.4%
Primary publication: Chapman PB, Hauschild A, Robert C, Haanen JB, Ascierto P, Larkin J, et al. Improved survival with vemurafenib in melanoma with BRAF V600E mutation. N Engl J Med. 2011;364(26):2507-16. PubMedDOI

Appears in

Sources

  1. Chapman PB, Hauschild A, Robert C, Haanen JB, Ascierto P, Larkin J, et al. Improved survival with vemurafenib in melanoma with BRAF V600E mutation. N Engl J Med. 2011;364(26):2507-16.

    PubMedDOI