Melanoma: FDA Approves Adjuvant Dabrafenib With Trametinib
The FDA based its approval on the results of the phase 3 COMBI-AD study.
The US Food and Drug Administration (FDA) approved dabrafenib with trametinib as an adjuvant therapy following complete resection for patients with BRAFV600E- or V600K-mutated melanoma with lymph node involvement, according to a press release.1
The FDA based its approval on results from the phase 3 COMBI-AD study (ClinicalTrials.gov Identification: NCT01682083), for which researchers randomly assigned 870 patients with advanced, high-risk melanoma after complete resection to receive dabrafenib 2 mg once daily plus trametinib 150 mg twice daily or placebo.
After a median follow-up of 2.8 years, the 3-year relapse-free survival rate was 58% vs 39% among patients in the combination therapy group vs placebo group, respectively (hazard ratio [HR], 0.47; 95% CI, 0.39-0.58; P < .001), representing a 53% reduced risk of disease recurrence or death.
Overall survival (OS) was prolonged in the combination arm as well: the 3-year OS rate among patients in the combination group was 86% compared with 77% in the placebo group (HR, 0.57; 95% CI, 0.42-0.79; P = .0006).2 This result did not, however, meet the pre-specified interim analysis boundaries.
The safety profile of the combination remained consistent with those previously reported for the components individually. No new safety signals were observed.
- Novartis receives FDA approval of Tafinlar + Mekinist for adjuvant treatment of BRAF V600-mutant melanoma [press release]. East Hanover, NJ: Novartis; April 30, 2018. https://www.novartis.com/news/media-releases/novartis-receives-fda-approval-tafinlarr-mekinistr-adjuvant-treatment-braf-v600-mutant-melanoma. Accessed May 1, 2018.
- Long GV, Hauschild A, Santinami M, et al. Adjuvant dabrafenib plus trametinib in stage III BRAF-mutated melanoma. N Engl J Med. 2017 Nov 9. doi: 10.1056/NEJMoa1708539 [Epub ahead of print]