Current Advances in Therapy for Metastatic Melanoma

Elaine      O’Donoghue; Dalia      Kamel; Bryan   T.   Hennessy

Abstract

2011 was a landmark year in the therapy for metastatic melanoma as it was the year that both Ipilmumab and Vemurafenib were approved by the FDA. Preceding this lay many years of frustration with no improvement in survival rates for 40 years. The prior standard therapy consisted of two main options, dacarbazine a non classic alkylating agent approved in the 1970s on the basis of overall response rates but having no benefit on survival and high dose IL2, approved in 1998 on the basis of durable complete response in a minority of patients. Thus the survival rates of patients with metastatic melanoma had remained largely unchanged since the 1970s with a median overall survival of 6 to 9 months. Metastatic melanoma is responsible for more than 75% of deaths from all forms of skin cancer, yet only represents less than 5% of all skin cancer diagnosis [1]. It is the most aggressive form of skin cancer and it is estimated that 76, 250 patients will be diagnosed in the United States in 2012 with 9,180 deaths [2]. The fruition of immunological and molecular research Ipilimumab, a CTLA4 antibody and Vemurafenib, a BRAF inhibitor in patients with BRAF mutation, have shown significant improvements in overall survival. With more targeted therapy options on the horizon these are significant times of hope for a disease which has proved so elusive in the past and has grown dramatically in incidence and annual mortality during the last few decades [3, 4]. This review will describe these new advances in targeted molecular and immunological therapies on the background of older therapies and also look at potential future therapy targets.

Keywords: BRAF inhibitors, Ipilimumab, MAPK pathway, MEK inhibitors, Metastatic melanoma, P13K/AKT pathway, somatic mutations.

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