FDA Grants Priority Review to Dabrafenib and Trametinib Combination for Resected Melanoma

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The drug combination was studied in patients with BRAFV600E/K mutations in the phase 3 COMBI-AD study, the results of which led to the FDA’s Priority Review designation.
The drug combination was studied in patients with BRAFV600E/K mutations in the phase 3 COMBI-AD study, the results of which led to the FDA’s Priority Review designation.

The US Food and Drug Administration (FDA) granted Priority Review to a supplemental New Drug Application (sNDA) for combined dabrafenib and trametinib as an adjuvant therapy for patients with BRAF-mutant stage III melanoma, according to a press release.1

The combination was studied in patients with BRAFV600E/K mutations in the phase 3 COMBI-AD study (ClinicalTrials.gov Identifier: NCT01682083), the results of which led to the FDA's Priority Review designation.

For COMBI-AD, 870 patients with completely resected melanoma were randomly assigned to receive adjuvant dabrafenib and trametinib (438 patients) or placebo (432 patients). Patients were stratified by variety of BRAF mutation.

The study met its primary endpoint of relapse-free survival (RFS): after a median follow-up of 2.8 years, the estimated 3-year RFS rates were 58% in the therapy group and 39% in the placebo group (hazard ratio, 0.47; P < .001).2

The 3-year overall survival rates were 86% in the therapy group and 77% in the placebo group (hazard ratio, 0.57; P = .0006), though this result did not meet the prespecified statistical boundary of P = .000019, according to The New England Journal of Medicine. The authors also noted that the “safety profile of dabrafenib plus trametinib was consistent with that observed with the combination in patients with metastatic melanoma.”

The FDA's decision about the sDNA is expected within 6 months.

Combination dabrafenib and trametinib are approved by the FDA for BRAF­V600E-mutant unresectable or metastatic melanoma and for BRAF­V600E-mutant metastatic non–small cell lung cancer.

References

  1. Novartis' combination therapy Tafinlar® + Mekinist® granted FDA Priority Review for the adjuvant treatment of stage III BRAF V600 mutation-positive melanoma [news release]. Basel, Switzerland: Novartis; December 22, 2017. https://www.novartis.com/news/media-releases/novartis-combination-therapy-tafinlarr-mekinistr-granted-fda-priority-review-adjuvant-treatment-stage-iii-braf-v600-mutation-positive-melanoma. Accessed December 26, 2017.
  2. Long GV, Hauschild A, Santinami M, et al. Adjuvant dabrafenib plus trametinib in stage III BRAF-mutated melanoma. N Engl J Med. 2017;377:1813-23. doi: 10.1056/NEJMoa1708539

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