The FDA granted regular approval to Tafinlar (dabrafenib) and Mekinist (trametinib) in combination for the adjuvant treatment of patients with melanoma with BRAF V600E or V600K mutations, as detected by an FDA-approved test, and involvement of lymph node, following complete resection.
The drugs are sponsored by Novartis Pharmaceuticals Corp.
Approval was based on COMBI-AD (NCT01682083), an international, multi-center, randomized, double-blind, placebo-controlled trial in 870 patients with stage III melanoma with BRAF V600E or V600K mutations, and pathologic involvement of regional lymph node. Patients were randomly allocated (1:1) to receive dabrafenib 150 mg twice daily in combination with trametinib 2 mg once daily or two placebos for up to 1 year.
The major efficacy outcome was relapse-free survival. Patients who received the combination treatment had a statistically significant improvement in RFS compared with those receiving placebo.
Patients in the combination arm experienced fewer recurrences/deaths at the time of data-cutoff: 38% (n=166), compared with 57% (n=248) in the placebo arm (hazard ratio 0.47; 95% confidence interval 0.39, 0.58; p<0.0001). The estimated median RFS was not reached for patients who received the combination therapy, compared with 16.6 months (95% CI: 12.7, 22.1) for those receiving placebo.
The recommended doses for the adjuvant treatment of melanoma are 150 mg of dabrafenib orally twice daily and 2 mg of trametinib orally once daily until disease recurrence or unacceptable toxicity, for up to one year.
FDA granted this application priority review. Dabrafenib in combination with trametinib was granted breakthrough therapy designation and orphan drug designation for this indication.
Tafinlar + Mekinist is the first oral targeted adjuvant combination therapy to demonstrate significant clinical benefit in patients with a BRAF V600 mutation, following complete surgical resection
In the EU, Tafinlar in combination with Mekinist is approved for patients with a BRAF V600 mutation in metastatic melanoma and non-small cell lung cancer.
In the US, Tafinlar in combination with Mekinist is approved for the treatment of patients with unresectable or metastatic melanoma with BRAF V600E or K mutations, as detected by an FDA-approved test, and for the adjuvant treatment of melanoma with BRAF V600E or K mutations and involvement of lymph node following complete resection. Tafinlar + Mekinist is also approved for BRAF V600E mutation-positive NSCLC.
