In a small study of patients with metastatic melanoma and the V600E BRAF gene mutation, 81% experienced a complete or partial regression of their disease when treated with the investigational drug PLX4032. These findings were recently published in The New England Journal of Medicine.

Melanoma is less common than non-melanoma skin cancer, but tends to be much more aggressive. Of the more than one million new diagnoses of skin cancer each year, roughly 62,000 involve melanoma. More than 8,000 people die of melanoma each year in the United States. What makes melanoma so dangerous is that it is more likely than other types of skin cancer to spread (metastasize) to other parts of the body.

In order to provide more individualized and more effective cancer therapy, much research has been focused on determining specific pathways involved in cancer cell growth or survival. The BRAF gene is known to play a part in cell growth, and mutations in BRAF are common in several cancer types. Research has indicated that 40-60% of melanomas carry a BRAF mutation. Roughly 90% of these BRAF mutations involve a specific mutation known as V600E. PLX4032 (also known as RG7204) is an investigational targeted therapy that has shown activity as an inhibitor of BRAF with the V600E mutation in preclinical studies.

In an extension of a Phase I clinical trial, 32 patients with metastatic melanoma and the V600E BRAF mutation received treatment with PLX4032 until their cancer progressed.  PLX4032 was given at the recommended Phase 2 dose.

  • Grade 2-3 adverse effects included rash, joint pain, nausea, sensitivity to light, fatigue, cutaneous squamous-cell carcinoma, itching, and hand-foot syndrome.
  • Of the 32 patients in the extension phase of this study, 2 experienced a complete response and 24 experienced a partial response. Median progression-free survival was reported to be more than 7 months. Overall, 81% of melanoma patients with the V600E BRAF mutation experienced complete or partial regression of their cancer.

The researchers concluded that PLX4032 was active in metastatic melanoma patients with the V600E BRAF mutation and had a tolerable side effect profile. PLX4032 is currently being evaluated in a randomized, controlled, Phase III (“BRAF Inhibitor in Melanoma” (BRIM3)) trial in previously untreated melanoma patients.

Reference:

Flaherty KT, Puzanov I, Kim KB, et al. Inhibition of Mutated, Activated BRAF in Metastatic Melanoma. The New England Journal of Medicine. 2010;363:809-819.

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