Novartis 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 being presented at the European Society for Medical Oncology (ESMO) 2016 Congress in Copenhagen.

"The three-year overall survival follow-up data from COMBI-v is remarkable because it is the second phase III study this year to demonstrate a significant long-term survival benefit for BRAF mutation-positive melanoma patients treated with Tafinlar + Mekinist combination therapy compared to BRAF inhibitor monotherapy," said Caroline Robert, MD, PhD, Head of Dermatology, Institute Gustave-Roussy. "The results of this trial continue to reinforce Tafinlar + Mekinist as a standard of care and sets a new benchmark for treating patients with BRAF V600 mutation-positive advanced melanoma."

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 arm.

"We are pleased to see the continued benefit of Tafinlar + Mekinist targeted combination therapy beyond three-years in another study," said Alessandro Riva, MD, Global Head, Oncology Development & Medical Affairs. "As we've come to understand, this combination of targeted inhibitors has demonstrated an unprecedented ability to block the known resistance pathways and extend overall survival for BRAF mutation-positive patients. These results underscore our commitment to advancing the practice of precision oncology and extending patients' lives through treatment options that target the root cause of their cancer."

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.

The safety results were consistent with the profile observed to date for the combination and consistent with the profile observed for vemurafenib monotherapy; no new safety concerns were observed.

COMBI-v is a two-arm, open-label, phase III study comparing the combination of Tafinlar + Mekinist with vemurafenib monotherapy in patients with BRAF V600E/K mutation-positive unresectable or metastatic melanoma. The primary endpoint of this study was OS. The Independent Data Monitoring Committee (IDMC) stopped the trial early based on efficacy results observed in the Tafinlar + Mekinist study arm as part of a planned interim analysis.

Advanced melanoma is the most serious and life-threatening type of skin cancer and is associated with low survival rates. Only about 20% of people will survive for at least five years following a diagnosis with late-stage disease. There are about 200,000 new cases of melanoma diagnosed worldwide each year, approximately half of which have BRAF mutations, a key target in the treatment of metastatic melanoma. Gene tests can determine whether a tumor has a BRAF mutation.

Combination use of Tafinlar + Mekinist in patients with unresectable or metastatic melanoma who have a BRAF V600 mutation is approved in the US, EU, Australia, Canada and other countries.

Tafinlar and Mekinist target different kinases within the serine/threonine kinase family - BRAF and MEK1/2, respectively - in the RAS/RAF/MEK/ERK pathway, which is implicated in non-small cell lung cancer (NSCLC) and melanoma, among other cancers. When Tafinlar is used with Mekinist, the combination has been shown to slow tumor growth more than either drug alone. The combination of Tafinlar + Mekinist is currently being investigated in an ongoing clinical trial program across a range of tumor types conducted in study centers worldwide.

The safety and efficacy profile of the Tafinlar + Mekinist combination has not yet been established outside of the approved indication.

Tafinlar and Mekinist are also indicated in more than 40 countries worldwide, including the US and EU, as single agents to treat patients with unresectable or metastatic melanoma with a BRAF V600 mutation.

The most common side effects of Tafinlar + Mekinist combination include fever, tiredness, nausea, headache, chills, diarrhea, rash, joint pain, high blood pressure, vomiting and cough. The incidence and severity of fever is increased when Mekinist is used in combination with Tafinlar.