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Bending the Curve Trial by Trial
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DREAMseq

DREAMseq (Doublet, Randomized Evaluation in Advanced Melanoma Sequencing) a Phase III Trial

Phase 3N = 265NCT02224781

Population
Treatment-naive BRAF V600-mutant metastatic melanoma; 265 patients enrolled in step 1 (133 arm A, 132 arm B per the full text), 73 went on to step 2
Design
Open-label randomised two-step phase 3 trial (ECOG-ACRIN EA6134): step 1 nivolumab plus ipilimumab (arm A) versus dabrafenib plus trametinib (arm B); at progression, patients entered step 2 on the alternate therapy (arm D or arm C). The abstract does not designate either arm as the control. Primary end point 2-year overall survival (step 1). The study was stopped early by the independent Data Safety Monitoring Committee because a clinically significant end point was achieved. The registry record lists 267 enrolled; the paper reports 265 enrolled in step 1.
Primary endpoint
OS
Arms
  • Nivolumab plus ipilimumab first (arm A) (experimental, n = 133): Step 1 nivolumab plus ipilimumab; at progression, step 2 dabrafenib plus trametinib (arm C)
  • Dabrafenib plus trametinib first (arm B) (experimental, n = 132): Step 1 dabrafenib plus trametinib; at progression, step 2 nivolumab plus ipilimumab (arm D)
People
Atkins MB, senior author Kirkwood JM
Show the numbers
Results reported for DREAMseq
EndpointAnalysisNivolumab plus ipilimumab first (arm A) / Dabrafenib plus trametinib first (arm B)ControlEffect
OSPatients starting step 1 (265 enrolled)primaryAtkins 202371.8% at 2 y (62.5–79.1%)—P=0.010Log-rank P value for 2-year overall survival, the primary end point. Median duration of response was not reached for arm A and 12.7 months for arm B (P<0.001).
PFSPatients starting step 1 (265 enrolled)primaryAtkins 2023median 11.8 months (5.9–33.5)—P=0.054Secondary end point; step 1 progression-free survival. No hazard ratio was found in the text read.
ORRPatients starting step 1 (265 enrolled)primaryAtkins 202346%—Objective response rates in step 2 were 47.8% (arm C) and 29.6% (arm D). Crossover occurred in 52% of patients with documented progression.
Results reported for DREAMseq
EndpointAnalysisNivolumab plus ipilimumab first (arm A) / Dabrafenib plus trametinib first (arm B)ControlEffect
OSPatients starting step 1 (265 enrolled)primaryAtkins 202371.8% at 2 y (62.5–79.1%)—P=0.010Log-rank P value for 2-year overall survival, the primary end point. Median duration of response was not reached for arm A and 12.7 months for arm B (P<0.001).
PFSPatients starting step 1 (265 enrolled)primaryAtkins 2023median 11.8 months (5.9–33.5)—P=0.054Secondary end point; step 1 progression-free survival. No hazard ratio was found in the text read.
ORRPatients starting step 1 (265 enrolled)primaryAtkins 202346%—Objective response rates in step 2 were 47.8% (arm C) and 29.6% (arm D). Crossover occurred in 52% of patients with documented progression.
Illustrative — modelled from reported values, not trial data. PFS, primary.
0%25%50%75%100%0510152025Months (modelled)
  • Nivolumab plus ipilimumab first (arm A) (experimental)
  • Dabrafenib plus trametinib first (arm B) (experimental)

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

Data table (modelled values)
MonthsNivolumab plus ipilimumab first (arm A)Dabrafenib plus trametinib first (arm B)
0100.0%100.0%
766.3%56.5%
1541.4%29.4%
2227.5%16.6%
3017.2%8.7%
Primary publication: Atkins MB, Lee SJ, Chmielowski B, Tarhini AA, Cohen GI, Truong TG, et al. Combination Dabrafenib and Trametinib Versus Combination Nivolumab and Ipilimumab for Patients With Advanced BRAF-Mutant Melanoma: The DREAMseq Trial-ECOG-ACRIN EA6134. J Clin Oncol. 2023;41(2):186-197. PubMedDOI

Appears in

Sources

  1. Atkins MB, Lee SJ, Chmielowski B, Tarhini AA, Cohen GI, Truong TG, et al. Combination Dabrafenib and Trametinib Versus Combination Nivolumab and Ipilimumab for Patients With Advanced BRAF-Mutant Melanoma: The DREAMseq Trial-ECOG-ACRIN EA6134. J Clin Oncol. 2023;41(2):186-197.

    PubMedDOI