Advances In Malignant Melanoma
From a melanoma detection point of view, the FDA just recently approved a device called MELA-find, which helps dermatologists decide whether to biopsy a lesion suspicious for melanoma. It is a computer-vision system that uses a hand held scanner. This system exhibited a 98.4% biopsy sensitivity compared to 78% biopsy sensitivity of the dermatologists. The devise has a high false positive rate in greater than 15% of the cases, but still better than a dermatologist false positive rate.
As far as surgical resection of melanoma, a new Scandinavian study that included almost 1,000 patients arrived to the conclusion that a 2 cm surgical margin is safe for melanomas thicker than 2 mm compared to a 4 cm margin that was previously recommended. The data had a 10-year follow up. The overall survival was equivalent in both arms. The advantage of a 2 cm margin is that the skin can be closed without grafting with subsequent decrease in morbidity.
As far as new therapies emerging in metastatic melanoma, we have several in phase II and III clinical trials that show promise. There is a vaccine (oncovex), which showed a 30% response rate and 12% complete response in stage III and IV melanoma by stimulating the immune system. A monoclonal antibody called ipilimumab doubled the one-year survival rate in stage IV melanoma by inhibiting the CTLA-4 molecule. Allovectin 7 is gene therapy injected directly into the tumors, which stimulates the immune system to attach the melanoma cells with 4-9% response rate. An inhibitor of BCL-2, a protein made by cancer cells called oblimersen genesense, has also shown to enhance the efficacy of chemotherapy by increasing apoptosis (cell death).
From a molecular fingerprinting point of view, it has been noted that 50% of melanoma patients carry a mutation in the BRAF gene that leads to cell division and growth. This mutation is a target for a kinase inhibitor called vemurafenib, which showed in phase III trials a response rate of 48%, much higher than chemotherapy approved for the disease.
Strides are being made in a disease that had few therapeutic options until recently, which is very important since the incidence of melanoma has rapidly increased over the last two decades.