The U.S. Food and Drug Administration (FDA) approved the combination of dabrafenib (Tafinlar) and trametinib (Mekinist) for the adjuvant treatment of patients with resected, stage III melanoma with BRAFV600 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 of 870 patients with stage III BRAF V600E/K mutation-positive melanoma treated with dabrafenib plus trametinib after complete surgical resection. Patients received the dabrafenib (150 mg twice daily) plus trametinib (2 mg once daily) combination (n = 438) or matching placebos (n = 432).
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).
Tafinlar is a BRAF inhibitor, while Mekinist is an MEK 1/2 inhibitor, and approval of the combination is based primary endpoints that were met in the COMBI-AD phase 3 study, which enrolled 870 patients with stage 3 BRA V600E/K mutation-positive melanoma who had undergone complete resection. Tafinlar + Mekinist reduced the risk of disease recurrence or death by 53% in comparison to placebo.
“Since the initial approval of Tafinlar and Mekinist in metastatic melanoma in 2013, the combination has become an important therapy for many patients carrying a BRAF mutation in both melanoma and lung cancers,” said Liz Barrett, CEO, Novartis Oncology. “Today’s FDA approval is an important milestone for patients who previously had limited treatment options in the adjuvant setting, and reflects our commitment to the ongoing development of this breakthrough treatment.”
“Prevention and early detection are important safeguards from melanoma, but that’s only half the picture. Melanoma is an aggressive cancer that can recur, particularly when it shows certain warning signs like increased depth, ulceration, or spread to the lymph nodes,” said Sancy Leachman, MD, PhD, Chair of the Department of Dermatology at OHSU School of Medicine.
“With proven treatment options for these patients, it is important for dermatologists to assure that appropriate patients are offered adjuvant treatment options – a ‘watch and wait’ approach is no longer the standard of care. Collaborating with a multidisciplinary care team of surgeons, pathologists and oncologists, and determining the right treatment based on the patient’s individual circumstances and mutational status is crucial to our patients’ care plans.”