The incidence of melanoma continues to increase. In early-stage disease, 5-year survival rates with surgical resection exceed 90%, however, stage III and IV disease has a higher risk of recurrence after resection, and many will ultimately die from metastatic melanoma. Since 2012 there has been a rapid increase in NICE approved therapy for patients with metastatic melanoma, with long-term survival now a reality for selected patient groups.
Novel oral agents targeting the MAP kinase pathway, specifically oncogenic mutations in BRAF (present in approximately 40% of melanomas), have enhanced outcomes.1, 2 Treatment with the BRAF inhibitor, dabrafenib, plus the mitogen-activated protein kinase kinase (MEK) inhibitor, trametinib, result in clinical benefit in over 90% of patients treated (median survival now approaching 3 years). This combination is routine practice in Northern Ireland, allowing treatment of severely unwell and symptomatic patients who previously may not have been suitable for chemotherapy, with often rapid resolution of symptoms within days to weeks.
Furthermore, this therapy has shown response rates in excess of 50% in patients with symptomatic brain metastases, improving symptoms and quality of life, providing options where once there were few and has largely superseded whole brain radiotherapy in this setting.3
More recently, the adjuvant COMBI-AD trial4 reported that patients with completely resected BRAF mutation melanoma treated with dabrafenib/trametinib for one year had improvement in the rate of relapse-free survival at 3 years of 58% vs. 39% with placebo, as well as improvement in survival at 3 years of 86% vs 77% . BRAF/MEK inhibitors in the adjuvant setting are expected to enter routine clinical practice following regulatory approvals.
Footnotes
UMJ is an open access publication of the Ulster Medical Society (http://www.ums.ac.uk).
References
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