Adjuvant therapy with dabrafenib and trametinib extended duration of survival without relapse of distant metastasis over placebo, with no apparent long-term effects, in patients with resected stage III melanoma, according to a 5-year follow-up of a phase 3 trial (N Engl J Med. 2020. doi:10.1056/NEJMoa2005493).
“In the previously reported primary analysis of this phase 3 trial, 12 months of adjuvant dabrafenib plus trametinib resulted in significantly longer relapse-free survival than placebo in patients with resected stage III melanoma with BRAF V600E or V600K mutations,” explained Reinhard Dummer, MD, University Hospital Zurich Skin Cancer Center, Zurich, Switzerland, and colleagues.
This 5-year follow-up of this phase 3 trial aimed to confirm the stability of the relapse-free survival benefit previously seen in the primary analysis.
The trial randomized 870 patients with resected stage III melanoma with a BRAF V600E or V600K mutation to receive 12 months of oral dabrafenib plus trametinib or 2 matched placebos. The primary end point of the trial was relapse-free survival.
The minimum duration of follow-up was 59 months. The 5-year percentage of patients alive without relapse was 52% (95% confidence interval [CI], 48 to 58) with dabrafenib plus trametinib compared with 36% (95% CI, 32 to 41) with placebo (hazard ratio [HR], 0.51; 95% CI, 0.42 to 0.61).
Additionally, the percentage of patients who were alive without distant metastasis was 65% (95% CI, 61 to 71) with dabrafenib plus trametinib versus 54% (95% CI, 49 to 60) with placebo (HR, 0.55; 95% CI, 0.44 to 0.70).
“In the 5-year follow-up of a phase 3 trial involving patients who had resected stage III melanoma with BRAF V600E or V600K mutations, 12 months of adjuvant therapy with dabrafenib plus trametinib resulted in a longer duration of survival without relapse or distant metastasis than placebo with no apparent long-term toxic effects,” Dr Dummer and colleagues concluded.—Janelle Bradley
