Adjuvant Dabrafenib Plus Trametinib Improved Long-Term Survival Among Patients With Advanced-Stage Melanoma Harboring BRAF V600 Mutations

According to final analysis results from the phase 3 COMBI-AD trial, adjuvant dabrafenib plus trametinib improved long-term recurrence-free and distant metastasis-free survival compared to placebo among patients with stage 3 melanoma harboring BRAF V600 mutations. 

As previously reported, “Five-year results of this trial showed that adjuvant therapy with dabrafenib plus trametinib resulted in longer relapse-free survival and distant metastasis–free survival than placebo among patients with BRAF V600–mutated stage III melanoma,” stated Georgina Long, MD, PhD, Melanoma Institute Australia, Wollstonecraft, Australia, and coauthors. However, “longer-term data were needed, including data regarding overall survival.”

In this double-blind study, 870 patients were randomized on a 1-to-1 basis to receive 150 mg of twice daily dabrafenib plus 2 mg of once daily trametinib (n = 438) or 2 matched placebos (n = 432) for a duration of 12 months. The primary end point was recurrence-free survival (RFS). Key secondary end points included overall survival (OS), distant metastasis-free survival, and safety. 

At the data cutoff point, median duration of follow-up was 8.33 years in the combination arm and 6.87 years in the placebo arm. At that time, median RFS was 93.1 months in the combination arm and 16.6 months in the placebo arm and estimated OS was 71% and 65%, respectively (hazard ratio [HR] 0.80; 95% confidence interval [CI], 0.62 to 1.01; P = .06). Estimated 10-year RFS was 48% in the combination arm and 32% in the placebo arm. Estimated 10-year distant metastasis-free survival was 63% in the combination arm and 48% in the placebo arm. Adverse events were reported among 97% of patients in the combination arm and 88% of patients in the placebo arm. Serious adverse events were reported by 41% and 13% of patients, respectively. No new safety signals were observed. 

“After nearly 10 years of follow-up, adjuvant therapy with dabrafenib plus trametinib was associated with better relapse-free survival and distant metastasis–free survival than placebo among patients with resected stage III melanoma,” concluded Dr Long et al. 

Source: 

Long GV, Hauschild A, Santinami M, et al. Final results for adjuvant dabrafenib plus trametinib in stage III melanoma. N Eng J Med. Published online: June 19, 2024. doi: 10.1056/NEJMoa2404139