For advanced melanoma patients with BRAF mutations, two pathway inhibitors are much better than one, according to a study presented at the European Society for Medical Oncology. The latest data confirm an estimated 45% of patients who received Tafinlar (dabrafenib) + Mekinist (trametinib) combination therapy are alive versus 31% of patients on BRAF monotherapy with with Zelboraf (vemurafenib).1
Of the more than one million new diagnoses of skin cancer each year, roughly 68,000 involve melanoma. More than 8,000 people die of melanoma each year in the United States. Melanoma is dangerous because it is more likely than other types of skin cancer to spread (metastasize) to other parts of the body.
Certain gene mutations affect cancer behavior, and a large and growing number of targeted therapies have been proven effective against cancers that contain these mutations. Many advanced melanomas, for example, contain mutations in the BRAF gene and can be treated with drugs known as BRAF or MEK inhibitors. The BRAF gene is known to play a part in cell growth, and mutations in BRAF are common in several types of cancer.
Approximately half of all melanomas carry a specific BRAF mutation known as V600E. This mutation produces an abnormal version of the BRAF protein that stimulates cancer growth. Some melanomas carry another BRAF mutation known as V600K.
Researches postulated that a combination of a BRAF inhibitor and a MEK inhibitor might mitigate the emergence of disease resistance that occurs with BRAF inhibition alone. Tafinlar and Mekinist target different kinases within the kinase family. 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.
About the COMBI-v Study
COMBI-v is a clinical trial that directly compared the combination of Tafinlar plus Mekinist with Zelboraf monotherapy in 704 patients with BRAF V600E/K mutation-positive unresectable or metastatic melanoma. The Independent Data Monitoring Committee stopped the trial early based on results observed wth Tafinlar plus Mekinist as part of a planned interim analysis.
Overall the response rates, duration of response and overall survival were improved with the combination therapy. The estimated three-year survival rate is 45% for patients receiving the combination of Tafinlar plus Mekinist compared with 31% of patients who received Zelboraf monotherapy Additionally, the estimated three-year progression-free survival rate was 24% for the combination arm and 10% for Zelboraf monotherapy.
- Robert C, Karaszewska B, Schachter J, et al. COMBI-v: A randomised, open-label, Phase III study comparing the combination of dabrafenib (D) and trametinib (T) with vemurafenib (V) as first-line therapy in patients (pts) with unresectable or metastatic BRAF V600E/K mutation-positive cutaneous melanoma. ESMO 2014. LBA4_PR.
- Robert. C, Karaszewska b, Schachter J, et al. Three-year estimate of overall survival in COMBI-v, a randomized phase 3 study evaluating first-line dabrafenib (D) + trametinib (T) in patients (pts) with unresectable or metastatic BRAF V600E/K-mutant cutaneous melanoma. Abstract #LBA40. 2016 European Society of Medical Oncology (ESMO) Annual Meeting, Copenhagen, Denmark.
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