These results from a sub-group of a Phase I/II study were recently presented at the 35th Congress of the European Society for Medical Oncology (ESMO).
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. Once melanoma has spread to the brain, median overall survival is four months, and currently, no available systemic therapies have been reported to improve survival.
Research has indicated that 40-60% of melanomas carry a BRAF mutation. The BRAF gene is known to play a part in cell growth. 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. Recently results from a Phase I study were published in the New England Journal of Medicine indicating that PLX4032 was active in metastatic melanoma patients with the V600E BRAF mutation and had a tolerable side effect profile. Another investigational agent that is being evaluated in melanoma patients with the V600E BRAF mutation is GSK2118436.
In the current Australian Phase I/II study, a sub-group of 10 melanoma patients with previously untreated metastases to the brain were evaluated following treatment with oral GSK2118436. Patients in this study had the V600E BRAF mutation and metastases that were 3mm or larger. Nine out of the ten patients had 20-100% reductions in the size of their brain metastases. Side effects reported in the dose-finding study were skin changes, low grade cutaneous squamous cell carcinoma, headache, nausea, fatigue, and vomiting.
Although this is a very small study, these results are encouraging for melanoma patients with brain metastases. Additional studies are warranted, and a Phase II study is planned.
 Long GV, Kefford RF, Carr PJA, et al. Phase 1/2 study of GSK2118436, a selective inhibitor of V600 Mutant (MUT) BRAF Kinase: Evidence of activity in melanoma brain metastases (METS). Presented at the 35th Congress of the European Society for Medical Oncology (ESMO), Milan, Italy, October 8-12, 2010. Abstract LBA 27.
 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.
 Kefford R, Arkenau H, Brown MP, et al. Phase I/II study of GSK2118436, a selective inhibitor of oncogenic mutant BRAF kinase, in patients with metastatic melanoma and other solid tumors*. J Clin Oncol*. 2010;28:15s (suppl; abstr 8503).
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