FDA Grants Breakthrough Designation to Adjuvant Melanoma Therapy

The FDA recently granted breakthrough therapy designation to a combination of dabrafenib (Tafinlar) plus trametinib (Mekinist) as an adjuvant treatment for stage 3 melanoma with a BRAF V600 mutation after resection, according to a press release.

Dabrafenib plus trametinib is being developed as the first adjuvant therapy specifically for patients with melanoma with a BRAF V600 mutation, according to Novartis.

Nearly half of the 200,000 new cases of melanoma diagnosed globally each year have BRAF mutations. Adjuvant therapy may be ideal for melanoma since a surgery-only approach can result in recurrence, according to the release.

The breakthrough designation is the result of positive findings from the phase 3 COMBI-AD clinical trial, which included 870 patients with stage 3 BRAF V600E/K mutation-positive melanoma. All patients underwent complete surgical resection prior to treatment with dabrafenib plus trametinib or placebo.

The primary endpoint was of relapse-free survival (RFS) was met after a follow-up of 2.8 years, according to Novartis. The researchers reported that RFS from the combination therapy was experienced across subgroups and disease stages.

Compared with placebo, treatment with the combination therapy was observed to reduce the risk of recurrence or mortality by 53%.

Secondary endpoints included overall survival, distant metastasis-free survival, freedom from relapse, and safety, according to the release.

The investigators reported that adverse events related to dabrafenib plus trametinib were consistent with previous studies. Approximately 97% of patients experienced an adverse event, with 26% leading to treatment discontinuation, according to Novartis.

The most common adverse events associated with the combination treatment were fever, nausea, diarrhea, fatigue, chills, headache, vomiting, joint pain, high blood pressure, rash, and cough.

Previously, dabrafenib plus trametinib received a breakthrough therapy designation in metastatic melanoma, non-small cell lung cancer (NSCLC), and anaplastic thyroid cancer, according to the release.

This combination has been approved to treat unresectable or metastatic melanoma with a BRAF V600 mutation and metastatic NSCLC with a BRAF V600E mutation.

"There is a need for more effective treatment options for stage III melanoma patients at a high risk of recurrence following surgical resection," said Samit Hirawat, executive vice president and head, Global Drug Development at Novartis Oncology. "We thank the FDA for recognizing the scientific advancement Tafinlar and Mekinist may provide in this adjuvant setting."