Novel therapies, such as immunotherapy and molecular-targeted therapies, are dramatically increasing survival rates in metastatic melanoma. Melanoma frequently is associated with somatic mutations, and each patient may have a unique collection of mutations resulting in the expression of antigens that bind to certain T-cell receptors, which serve as targets for inhibitor immunotherapy.
Ipilimumab and nivolumab are monoclonal antibodies directed against negative regulators of T-cell activation. When ipilimumab and nivolumab bind to their receptors, feedback inhibition is prevented, which results in an immune response against the tumor. In a trial of 53 patients with advanced melanoma treated with both drugs, the overall survival rate at 1 and 2 years was 94% and 88%, respectively.13
Dabrafenib and trametinib. Mutations that activate the serine/threonine kinase gene, BRAF, are present in approximately 40% to 60% of advanced melanomas and lead to clonal expansion and tumor progression.14,15 Inhibition of BRAF produces rapid tumor regression—even in extensive disease. Treatment with dabrafenib, a BRAF inhibitor, and trametinib, a mitogen-activated protein kinase inhibitor, has been shown to be superior to a BRAF inhibitor alone and is associated with a survival rate of 72% at 1 year.16
Our patient. Seven months after enrolling in the clinical trial with ipilimumab and nivolumab, our patient developed brain metastases and was withdrawn from the trial. A resection of her brain metastases and radiation therapy followed. The patient was then started on molecular-targeted therapy with dabrafenib and trametinib. Twelve weeks later, a repeat CT scan of the chest, abdomen, and pelvis demonstrated an interval decrease in the size of the majority of the metastatic lesions, and a repeat brain MRI showed no additional metastases.
More than 4 years after her diagnosis, our patient remains on dabrafenib and trametinib therapy and her metastatic lesions to the lung and liver remain stable.
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