The US Food and Drug Administration (FDA) has approved the combination of dabrafenib (Tafinlar, Novartis) and trametinib (Mekinist, Novartis) for the adjuvant treatment of patients with resected, stage III melanoma with BRAF V600 mutations.
The combination is already approved for the treatment of metastatic melanoma in patients who are positive for these mutations.
The new approval is based on findings from the COMBI-AD phase 3 study, which were first presented at the European Society for Medical Oncology (ESMO) 2017 Congress and were simultaneously published online in the New England Journal of Medicine.
The double-blind, placebo-controlled study included a total of 870 patients with stage III, BRAF V600E/K-mutant melanoma who had previously undergone complete surgical resection and were disease-free after surgery.
Patients were randomly assigned to receive either the combination of dabrafenib 150 mg twice daily and trametinib 2 mg once daily (n = 438) or matching placebo (n = 432) for 12 months. Patients were also stratified on the basis of BRAF mutation (V600E vs V600K) and stage (IIIA vs IIIB vs IIIC). The primary endpoint was relapse-free survival (RFS).
At a median follow-up of 2.8 years, the estimated 3-year RFS rate was 58% in the combination therapy group and 39% in the placebo group (hazard ratio for relapse or death, 0.47; 95% confidence interval [CI], 0.39 – 0.58; P < .001).
The RFS benefit in the combination therapy group was observed across all patient subgroups.
This is the first effective oral targeted therapy combination that prevents relapse among patients with BRAF-mutated melanoma that has spread to lymph nodes, said investigator John Kirkwood, MD, director of Melanoma and Skin Cancer, University of Pittsburgh, Pennsylvania, in a company press statement.
The safety profile of dabrafenib plus trametinib was consistent with that observed with the combination in patients with metastatic melanoma. No new toxic effects were reported in the phase 3 trial.
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