FDA Grants Breakthrough Therapy Designation to Adjuvant Dabrafenib Plus Trametinib for Melanoma
Dabrafenib plus trametinib is the first adjuvant therapy indicated specifically for melanoma with the BRAFV600 mutation.
The US Food and Drug Administration (FDA) granted Breakthrough Therapy Designation (BTD) to combination dabrafenib and trametinib as adjuvant treatment for patients with BRAFV600 mutation–positive stage III melanoma following complete resection.
Dabrafenib plus trametinib previously received BTD for metastatic melanoma, non–small cell lung cancer (NSCLC), and anaplastic thyroid cancer (ATC), though this is the first adjuvant therapy indicated specifically for melanoma with the BRAFV600 mutation.
The FDA granted BTD based on evidence from the phase 3 COMBI-AD study (ClinicalTrials.gov Identifier: NCT1682083), for which researchers randomly assigned 870 patients with stage III melanoma who underwent complete resection to receive dabrafenib plus trametinib or placebo for 1 year.
At the median follow-up of 2.8 years, patients in the treatment arm had a relapse-free survival rate of 58% compared with 39% in the placebo arm (hazard ratio [HR], 0.47; 95% CI, 0.39-0.58; P < .001).
The 3-year overall survival rate was 86% and 77% among patients in the combination-treatment arm and the placebo arm, respectively (HR, 0.57; 95% CI, 0.42-0.79; P = .0006), but this finding did not meet the pre-specified interim analysis boundary of P = .000019.
Ninety-seven percent of patients who received the treatment combination experienced adverse events (AEs); 41% of patients reported grade 3 to 4 AEs and 26% of patients reported an AE that led to treatment discontinuation. The toxicity profile was consistent with previously reported findings for dabrafenib plus trametinib.
- Breakthrough therapy designation for stage III BRAF V600 mutation-positive melanoma patients [news release]. Basel, Switzerland: Novartis; October 23, 2017. https://www.novartis.com/news/media-releases/novartis-combination-adjuvant-therapy-tafinlarr-mekinistr-receives-fda. Accessed October 23, 2017.