Dabrafenib–Trametinib Combination Receives FDA Approval for Adjuvant Treatment of Malignant Melanoma

On 30 April 2018, by the United States Food and Drug Administration FDA, BRAF mutation -positive patients with lymph node metastasis and the skin cancer malignant melanomawere granted approval for adjuvant (postoperative preventive) treatment with the combined use of dabrafenib (brand name Tafinlar) and trametinib (Mekinist).

- Related topic: What is a BRAF mutation? Which cancers can be BRAF-positive?

The approval is based on an international, multicenter, randomized, double-blind trial involving patients with regional lymph node involvement and BRAF V600E or V600K mutation-positive stage III melanoma, 870 patients in total, with a placebo -controlled design, a clinical trial called COMBI-AD. Patients were randomly divided into two groups: one received dabrafenib 2 times daily at 150 mg along with trametinib 1 time daily at 2 mg, while the other received placebo twice daily for up to 1 year.

Treatment effectiveness was assessed primarily by measuring relapse-free survival . Relapse-free survival was defined as the time from the start of treatment until disease recurrence (local, regional or distant metastasis), a new primary melanoma, or death from any cause.

Patients receiving combination treatment had a statistically significant improvement in relapse-free survival compared with those receiving placebo. Patients in the combination arm experienced fewer recurrences/deaths: %38 versus %57. For patients receiving combination treatment, estimated median relapse-free survival was not reached because most patients continued to respond, while median relapse-free survival in the placebo group was 16.6 months.

In the COMBI-AD trial, in at least% 20 of patients receiving the combination, the most common side effectswere fever, lethargy, nausea, headache, rash, chills, diarrhea, vomiting, arthralgia and myalgia . Side effects resulting in dabrafenib discontinuation, dose reduction or interruption occurred in %25, %35 and %66 of patients, respectively; fever and chills were the most common for each. Side effects resulting in trametinib discontinuation and discontinuation occurred in %24 and %54 of patients, respectively; fever and chills were the most common for each. Adverse reactions leading to trametinib dose reduction occurred in %23 of patients; the most common were fever and decreased ejection fraction (the heart’s pumping strength).

For adjuvant treatment of melanoma, the recommended doses are oral tablets, for up to 1 year: dabrafenib 150 mg twice daily and trametinib 2 mg once daily. 

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