COMBI-AD
Trial question
What is the role of adjuvant dabrafenib plus trametinib in patients with resected stage III melanoma?
Study design
Multi-center
Double blinded
RCT
Population
Characteristics of study participants
55.0% female
45.0% male
N = 870
870 patients (482 female, 388 male).
Inclusion criteria: patients with resected stage III melanoma with BRAF V600 mutation.
Key exclusion criteria: mucosal or ocular melanoma; presence of unresectable in-transit metastases; distant metastatic disease; prior systemic anti-cancer treatment and radiotherapy for melanoma; cardiovascular risk; retinal vein occlusion or central serous retinopathy.
Interventions
N=438 dabrafenib plus trametinib (dabrafenib 150 mg BID plus trametinib 2 mg once daily).
N=432 placebo (two matching placebos).
Primary outcome
Median relapse-free survival
93.1 months
16.6 months
93.1 months
69.8 months
46.5 months
23.3 months
0.0 months
Dabrafenib plus
trametinib
Placebo
Significant
increase ▲
Significant increase in median relapse-free survival (93.1 months vs. 16.6 months; HR 1.92, 95% CI 1.59 to 2.33).
Secondary outcomes
No significant difference in overall survival at 8 years (71% vs. 65%; HR 1.25, 95% CI 0.99 to 1.61).
Significant increase in distant-metastasis-free survival at 10 years (63% vs. 48%; HR 1.79, 95% CI 1.41 to 2.27).
No significant difference in melanoma-specific survival (77% vs. 74%; HR 1.28, 95% CI 0.98 to 1.69).
Safety outcomes
Significant difference in incidence of primary or secondary cancer (3.98 events per 100 patient-years vs. 2.61 events per 100 patient-years).
Conclusion
In patients with resected stage III melanoma with BRAF V600 mutation, dabrafenib plus trametinib was superior to placebo with respect to median relapse-free survival.
Reference
Georgina V Long, Axel Hauschild, Mario Santinami et al. Final Results for Adjuvant Dabrafenib plus Trametinib in Stage III Melanoma. N Engl J Med. 2024 Nov 7;391(18):1709-1720.
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