Novartis has announced that the European Commission (EC) has approved Tafinlar® (dabrafenib) in combination with Mekinist® (trametinib) for the adjuvant treatment of stage III patients with BRAF V600 mutation-positive melanoma after complete surgical resection.
This approval is the third for Tafinlar in combination with Mekinist in Europe across a variety of tumour types identified with a high level of BRAF mutation. To date, more than 60,000 patients worldwide have been treated with the combination therapy across four indications.
The approval is based on results from the Phase III COMBI-AD global study, which enrolled more than 870 patients with stage III, BRAF V600E/K-mutant melanoma without prior anticancer therapy, and who were randomised within 12 weeks of complete surgical resection. In the primary analysis, and after a median follow-up of 2.8 years, the primary endpoint was met, with the combination therapy significantly reducing the risk of disease recurrence or death by 53% vs. placebo. Based on updated data, with an additional 10 months of follow-up compared to the primary analysis (minimum follow-up of 40 months), treatment with the combination therapy reduced the risk of recurrence or death by 51% vs. placebo.
The BRAF gene belongs to a class of genes known as oncogenes and provides instructions for making a protein that helps transmit chemical signals from outside the cell to the cell’s nucleus. This protein is part of a signalling pathway known as the RAS/MAPK pathway, which controls several important cell functions. Specifically, the RAS/MAPK pathway regulates the growth and division (proliferation) of cells, the process by which cells mature to carry out specific functions (differentiation), cell movement (migration) and the self-destruction of cells (apoptosis). Chemical signalling through this pathway is essential for normal development before birth. When mutated, oncogenes have the potential to cause normal cells to become cancerous. During cancer treatment, targeted therapies may inhibit the mutation from occurring, thus slowing the growth of the cancer tumour.
Liz Barrett, CEO, Novartis Oncology commented, “Novartis’ deep therapeutic knowledge and our ability to apply novel approaches to the development of new medicines has resulted again in a new treatment advance for melanoma patients. The European approval of the Tafinlar and Mekinist combination illustrates Novartis’ continued efforts to re-imagine cancer by providing a highly effective, targeted therapy for earlier-stage melanoma patients.”