Melanoma is notoriously not responsive to chemotherapy and radiation therapy. Interferon and Interlukin 2 were the first therapies that had some efficacy in metastatic melanoma but unfortunately the response rate was very low at around 10%. Most recently with better understanding of the biology of melanoma a new class of drugs was developed with a much better response rate.
Dabrafenib (tafinalar) and trametinb (mekenist) were two oral drugs recently FDA approved. Dabrafenib is a BRAF inhibitor which means it targets melanomas that express the BRAF V600E gene mutation. Sorafenib was FDA approved in 2005 and vemurafenib (zelborif) was FDA approved in 2011 for melanoma.
The major side effects from BRAF inhibitors involve the skin folliculits, hand foot syndrome, hair changes, photosensitivity, hyperkeratosis. Diarrhea can also occur. At least 50% of melanomas have the BRAF mutation.
Trametinib is a MEK inhibitor (mitogen activated extracellular signal related kinase inhibitor). It was tested in patients who failed other treatments and it improved disease free survival as well as over all survival. The most common side effects are diarrhea, rash and swelling. Trametinb used in combination with dafrasenib seems to have less side effects and more efficacy.
Data presented at ASCO 2013 showed that nivolumab, an experimental immunotherapy, showed 30% response rate in heavily pretreated patients. Responses occurred rapidly and were long lasting. The median survival was longer than currently approved drugs. Major strides have been made and continue to be made in this very difficult to treat disease.