October 2nd, 2014

BRAF/MEK Inhibitor Combination Impressive in Melanoma Trials


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.

In order to evaluate this treatment approach a clinical study was designed that enrolled 495 patients with previously untreated BRAF mutation-positive melanoma. The CoBRIM study compared Zelboraf® (vemurafenib) plus the MEK inhibitor cobimetinib to treatment with Zelboraf alone.

The combination therapy resulted in improved response to treatment, prolonged time to cancer progression, and a reduction in mortality. The combination was very well tolerated, with a low rate of serious adverse events, and less skin toxicity was reported with the combination than was seen with Zelboraf alone.

One of the study authors, Dr. Grant McArthur of the Peter MacCallum Cancer Center in Austrailia stated, “This study provides clear and definitive evidence that cobimetinib combined with Zelboraf results in improved progression-free survival and objective response rates, and our preliminary overall survival analysis is promising,”

Reference: McArthur G, Ascierto P, Larkin J, et al. Phase 3, double-blind, placebo-controlled study of vemurafenib versus vemurafenib + cobimetinib in previously untreated BRAFV600 mutation-positive patients with unresectable locally advanced or metastatic melanoma (NCT01689519). ESMO 2014, LBA5_PR.

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Tags: BRAF, cobimetinib, cobrim, mek, Melanoma, News, Recurrent Melanoma, Stage III Melanoma, Stage IV Melanoma, Uncategorized, vemurafenib, zelboraf