ARTICLE

Full text free online at www.australianprescriber.com Medical management of malignant melanoma SUMMARY The treatment and outcomes for people with metastatic melanoma have changed considerably in the past few years with the introduction of targeted anticancer drugs. About half of the patients with metastatic melanoma will have activating mutations in the BRAF gene. These people may benefit from a BRAF inhibitor (vemurafenib or dabrafenib) or a MEK inhibitor (trametinib). Addition of a MEK inhibitor to a BRAF inhibitor improves progression-free survival and alters the adverse effect profile. Ipilimumab is another drug indicated for metastatic melanoma. It works by altering the patient’s own immune response to the tumour. Toxicities are common with these drugs and include arthralgias, fatigue, photosensitivity, squamous cell carcinomas, fever, diarrhoea, pruritus and immune-related adverse effects. disease is incurable and results in a significant loss of life – for example, 365 deaths from metastatic melanoma were registered in Queensland in 2010.1,3 The most commonly used drugs in melanoma were dacarbazine and fotemustine. These have been trialled extensively and have complete and partial response rates * of around 10%. They do not prolong survival. Until 2010, there were no significant advances in improving survival for metastatic melanoma – the median overall survival of nine months had not changed in 30 years. However, the introduction of targeted anticancer drugs has substantially altered the treatment and outcomes for patients with melanoma. Melanoma mutations Systemic therapy options for metastatic melanoma currently depend on whether the patient’s tumour expresses the BRAF mutation. These mutations occur in the mitogen-activated protein (MAP) kinase pathway (see Fig.). Acquired BRAF mutations lead to the expression of an abnormal protein kinase that mediates continuous cell growth and malignant transformation. BRAF mutations were found to be frequent in melanoma in 2002.4 About 40–60 % of patients have an activating BRAF mutation in their metastatic * A complete response is defined as the disappearance of all lesions on imaging, and a partial response is defined as a 30 % reduction in the size of target lesions