The US Food and Drug Administration (FDA) has granted priority review to the combination of dabrafenib (Tafinlar) and trametinib (Mekinist) for the adjuvant treatment of patients with stage III melanoma with BRAF V600E or V600K mutations after complete disease resection. The combination was granted Breakthrough Therapy designation earlier this year.
The FDA’s decision was based on data from the COMBI-AD phase III study evaluating the drug combination presented at the 2017 European Society for Medical Oncology (ESMO) Congress. Results presented there showed that 1 year of combination treatment reduced the risk for disease recurrence or death by 53% among this patient population.
The study included 870 patients with treatment-naive disease. All patients were within 12 weeks of resection and were randomly assigned to the combination of dabrafenib 150 mg twice daily plus trametinib 2 mg once daily or placebo. Treatment was given for 1 year.
With a median follow-up of 2.8 years, the median relapse-free survival was not yet reached in patients assigned dabrafenib plus trametinib compared with 16.6 months for placebo (hazard ratio [HR], 0.47; 95% CI, 0.39–0.58). This benefit occurred across all patient subgroups.
Combination treatment also resulted in an improvement in overall survival compared with placebo (HR, 0.58; 95% CI, 0.42–0.79). The 3-year overall survival rate was 86% for combination therapy compared with 77% for placebo (P = .0006). However, this did not cross the predefined interim analysis boundary of P = .000019 to claim statistical significance.
The majority (97%) of patients assigned to combination treatment had adverse events; 41% of patients had grade 3/4 events. About one-quarter of patients (26%) had adverse events that led to discontinuation of treatment compared with 3% of patients assigned to placebo.
“The FDA's decision to grant Tafinlar in combination with Mekinist Breakthrough Therapy designation and Priority Review designation validates the potential of the combination to have a significant impact on the lives of melanoma patients treated in the adjuvant setting,” said Samit Hirawat, MD, head of Oncology Global Drug Development at Novartis, in a press release. “There remains a need to address the high risk of recurrence seen in these patients and improve the quality of care they receive.”