Latest melanoma drug approvals: adjuvant dabrafenib plus trametinib

New drug combination: adjuvant dabrafenib plus trametinib for BRAF-mutant stage III melanoma

The European Commission approved the combination of dabrafenib plus trametinib (TafinlarĀ® and MekinistĀ® by Novartis) for the adjuvant therapy of complete surgically resected stage III melanoma patients with BRAFV600 mutation.

The dual targeting of the hyper-activated MAPK pathway by dabrafenib (which blocks the signaling pathway of the V600E-mutated BRAF molecule) and by trametinib (which targets the activity of MEK in order to block the signaling from the V600E or V600K-mutated BRAF molecule in coordination with the MEK molecule) is expected to prolong relapse-free survival of melanoma patients.

The drug combination was approved to treat completely resected stage III melanoma patients with the V600E or V600K mutation in the BRAF gene.

Study outcomes

The approval was based on the phase III multicenter COMBI-AD trial (NCT01682083) with over 870 enrolled stage III melanoma patients. In this global study, two MELGEN research sites were among the participating centers: the Department of Dermatology at the University Hospital of Essen (Germany) lead by Prof. Dirk Schadendorf, and the Department of Dermatology at the University Hospital Zurich (Switzerland) lead by Prof. Reinhard Dummer.

Patients were randomized 1:1 to receive dabrafenib (150 mg twice daily) plus trametinib (2 mg once daily) or two matched placebo tablets.

The primary end-point measure of the trial was relapse-free survival; the secondary end-point measure was overall survival (OS). According to the research results, the estimated 3-year relapse-free survival was 58% in the combination arm (dabrafenib plus trametinib) vs. 39% in the control arm (placebo) with hazard ratios for relapse or death of 0.47 (95% CI: 0.39-0.58, P<0.0001). The 3-year OS rate was 86% in the combination arm (dabrafenib plus trametinib) vs. 77% in the control arm (placebo) with a hazard ratio for death of 0.57 (95% CI: 0.42-0.79, P=0.0006). Overall, the combination therapy significantly reduced the risk of recurrence or distant metastasis in stage III melanoma.

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Long GV, Hauschild A, Santinami M, et al. Adjuvant Dabrafenib Plus Trametinib for Stage III BRAF V600E/K-Mutant Melanoma. New England Journal of Medicine. 2017.