COMBI-AD Trial: Longer-Term Follow-up of Adjuvant Dabrafenib Plus Trametinib in Resected BRAF V600–Mutant Stage III Melanoma
As reported by Hauschild et al in the Journal of Clinical Oncology, longer-term follow-up of the phase III COMBI-AD trial has confirmed improved relapse-free survival with adjuvant dabrafenib (Tafinlar) plus trametinib (Mekinist) vs placebo in resected BRAF V600–mutant stage III melanoma. In the primary analysis from the trial, with median follow-up of approximately 34 months, the combination treatment improved relapse-free survival, the primary endpoint, with a hazard ratio (HR) of 0.47 (P < .001).
Updated Results
In the double-blind trial, 870 patients were randomly assigned to receive 12 months of dabrafenib 150 mg twice daily plus trametinib 2 mg once daily (n = 438) or placebo (n = 432).
After median follow-up of 44 months in the dabrafenib plus trametinib group and 42 months in the placebo group, estimated relapse-free survival rates were 59% vs 40% at 3 years and 54% vs 38% at 4 years (HR = 0.49, 95% confidence interval [CI] = 0.40–0.59). Subgroup analysis indicated similar relapse-free survival benefit of dabrafenib plus trametinib irrespective of baseline factors, including disease stage using both American Joint Committee on Cancer 7th and 8th editions (eg, HRs = 0.58, 0.49, and 0.46 for stages IIIA, B, and C on 7th edition), nodal metastatic burden (HR = 0.40 for 2 to 3 nodal metastatic masses, HR = 0.53 for ≥ 4), and tumor ulceration (HR = 0.53 for no baseline ulceration, HR = 0.45 for baseline ulceration).
The investigators concluded, “Longer follow-up confirmed [relapse-free survival] benefit with dabrafenib plus trametinib. Subgroup analysis suggested that dabrafenib plus trametinib benefited patients regardless of baseline factors.”
Georgina V. Long, MD, of the Melanoma Institute Australia, University of Sydney, is the corresponding author for the Journal of Clinical Oncology article.
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