It has been a watershed year in melanoma therapy, with FDA approval of two new drugs for advanced melanoma. The most dramatic clinical responses have been to BRAF targeted therapy, which capitalizes on the discovery of a specific driver mutation present in many melanomas, and was discussed in detail in the last issue of The Melanoma Letter.
Other driver mutations are now being targeted in tumor-directed therapies. One such mutation found in a subset of melanoma patients involves cKit. Targeting the cKit mutation offers similar hopes of controlling metastatic melanomas that harbor the defect. In the lead story in this issue, Dr. Richard Carvajal shares with us current knowledge on the use of imatinib and other developing drugs as targeted therapy for melanomas harboring the cKit driver mutation.
On the other side of the equation, it has long been appreciated that the immune system plays an important role in preventing and controlling cancer. Harnessing the immune system to treat cancer has been the goal of immunotherapists for decades, and therapies like IL-2 and adoptive T cell transfer have demonstrated encouraging evidence of the principle that even patients with advanced metastatic cancer can be cured with immunotherapy. Unfortunately, these immunotherapies are associated with considerable toxicity and are applicable for only a small minority of patients. A recent breakthrough in melanoma immunotherapy was the approval of ipilimumab (Yervoy), an immune checkpoint blockade inhibitor, which is more broadly applicable and has had significant life-extending benefits.
Along with immunotherapy for advanced disease, there have been decades of research in adjuvant immunotherapy. The concept is to treat patients without clinical evidence of disease who are nonetheless at very high risk of developing distant metastases; the hope is to forestall or prevent this from happening. Typically, these patients have been surgically rendered ‘free of disease’ by removal of lymph node metastases or thick primary melanomas. The only FDA-approved immunotherapy for these patients is interferon, the most broadly and extensively tested adjuvant therapy for melanoma. The varied formulations, doses, and timing of interferon in multiple clinical trials make interpretation of the data a bit challenging. In this issue of The Melanoma Letter, Drs. Ahmad A. Tarhini and John Kirkwood present an excellent review and summary of these many trials, including the latest information on the recently FDA-approved pegylated version of interferon.