COMBI-v BRAF/MEK Inhibitor Combination Trial Impressive in Melanoma
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 Meeting this week.
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.
The COMBI-v trial compared the combination of the BRAF inhibitor dabrafenib (Tafinlar) plus the MEK inhibitor Mekinist (trametinib) with Zelboraf (vemurafenib) alone in 704 treatment-naive patients with the BRAF V600 mutation.
Overall response rates, duration of response and overall survival were improved with combination therapy. The median overall survival was 17.2 months with Zelboraf alone and had not been reached in the Tafinlar/ Mekinist treated patients. The preplanned interim analysis showed a 31% reduction in mortality among patients on the combination, and a 44% reduction in the risk of progression, compared to Zelboraf monotherapy.
Reference: 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.
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