COMBI-v study of Tafinlar (dabrafenib) + Mekinist (trametinib) success in BRAF V600 mutation-positive advanced melanoma. Novartis

Novartis has announced data from the Phase III COMBI-v study demonstrating an overall survival (OS) and a progression-free survival benefit for patients with BRAF V600 mutation-positive advanced melanoma when treated first-line with the combination of Tafinlar (dabrafenib) + Mekinist (trametinib) compared to vemurafenib monotherapy.

The results of this study, which was conducted in 704 patients, are presented at the European Society for Medical Oncology (ESMO) 2016 Congress in Copenhagen. Results from the COMBI-v study found the estimated three-year survival rate to be 45% of patients receiving the combination of Tafinlar + Mekinist (95% CI, 39.1%-49.8%) compared with 31% of patients who received vemurafenib monotherapy (95% CI, 26.1%-36.4%). There were 34 patients who crossed over from the vemurafenib monotherapy arm to the combination arm after the combination demonstrated a significant OS benefit in a prior analysis. Additionally, the estimated three-year progression-free survival rate was 24% (95% CI, 19.4%-28.8%) for the combination arm and 10% (95% CI, 5.9%-14.5%) for the vemurafenib monotherapy mark. At three years of follow up, the combination of Tafinlar + Mekinist continued to demonstrate a benefit on the measures of duration of response (DoR) and overall response rate (ORR), in line with results seen at the two-year follow up analysis.

Comment: Currently, Zelboraf (vemurafenib) is used as first line treatment for advanced BRAF V600 mutation positive melanoma. Following progression, ipilimumab may be used as second line treatment. The Tafinlar+ Mekinist combination is expected to replace Zelboraf with advantages in efficacy and less toxicity.