Combination BRAF, MEK Inhibitor Improves Melanoma Survival

Novartis recently announced positive results from a phase 2 clinical trial, which demonstrated a survival benefit for certain patients with metastatic skin cancer treated with dabrafenib (Tafinlar) + trametinib (Mekinist).

The combination therapy of BRAF and MEK inhibitors was observed to benefit patients with BRAF V600 mutation-positive metastatic melanoma. The results from the 5-year analysis is the longest follow-up of the combination treatment among these patients, according to a presentation at the Annual Meeting of the American Society of Clinical Oncology.

Included in the study were 162 patients with BRAF V600 mutation-positive metastatic melanoma administered either dabrafenib (150-mg twice per day) monotherapy or dabrafenib + trametinib combination therapy (150-mg twice per day; 2-mg once per day).

After 5 years, the investigators reported that 37% of patients remained in the study: 7 in the monotherapy cohort and 13 in the combination therapy cohort.

The researchers discovered that overall survival was higher among patients treated with the combination therapy compared with those treated with the monotherapy.

Overall survival rates for the monotherapy cohort were 23% at 4 years and 21% at 5 years, while overall survival rates were 30% at 4 years and 18% at 5 years for the combination therapy, according to the study. The authors said that this trend suggests that survival stabilized over time.

Progression-free survival for the monotherapy cohort was at 3% for both years, but was at 13% among patients treated with the combination therapy. This trend also indicates stabilization, according to the study.

The authors noted that 83% of patients in the monotherapy group went on to receive the combination therapy and their outcomes were included under the monotherapy reporting.

"These recent results from the longest follow-up of a BRAF and MEK inhibitor targeted study show that a significant cohort of patients with metastatic melanoma positive for the BRAF V600 mutation can achieve long-term survival with Tafinlar + Mekinist combination therapy," said lead investigator Jeff Weber, MD, PhD. "This combination of targeted therapy should be considered by physicians when making treatment decisions."

The researchers reported that the safety profile of the combination was consistent with other studies. Additional follow-up did not indicate new safety concerns, according to the study.

Dabrafenib + trametinib is indicated to treat patients with unresectable or metastatic melanoma who have a BRAF V600 mutation. Dabrafenib + trametinib target the BRAF and MEK 1/2 kinases, respectively, in the RAS/RAF/MEK/ERK pathways, which are involved with multiple cancers, according to the study.

In combination, the drugs slow cancer growth more substantially than either drug administered as a monotherapy.

Dabrafenib + trametinib has received approval in more than 50 countries as monotherapies to treat patients with unresectable or metastatic melanoma with a BRAF V600 mutation.

"These data demonstrate the long-term benefit of Tafinlar in combination with Mekinist for certain patients living with metastatic melanoma," said Vas Narasimhan, global head Drug Development and chief medical officer at Novartis. "We are gratified to see these data showing that patients can benefit long-term from Tafinlar + Mekinist, and we look forward to evaluating additional Phase III long-term survival data."