The next few years may show that when the novel therapeutics reviewed in this article are used in thoughtful combinations, a new standard of care for the treatment of advanced melanoma will emerge. As more understanding is gained on the different signaling pathways for tumor cell growth and mechanisms of action of the different classes of drugs, the ability to identify different subsets of patients with differentially dysregulated oncogenic signaling pathways may allow for more individualized treatments of advanced melanoma in the near future, which will ultimately translate into improved survival.
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Identifying genetic mutations in melanoma has permitted targeted therapies to impact treatment and survival of melanoma patients.
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Harnessing the activity of the immune system has been an effective means of impacting on the treatment and survival of melanoma patients.
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Combining targeted therapies and immunotherapeutic agents is the future of melanoma research.
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Despite the successful impact of vemurafenib and ipilimumab on the treatment and survival of melanoma patients, clinical trials must remain the “gold standard” in order to further improve patient outcomes.
Introduction
Disseminated malignant melanoma has been unresponsive to standard treatment and was associated with a dismal prognosis, with 5-year survivals at 10% to 25% before the Food and Drug Administration (FDA) approval of 2 novel therapies in 2011. According to Surveillance, Epidemiology, and End Results (SEER) data, approximately 4% of melanomas are metastatic at the time of diagnosis. Systemic chemotherapy for disseminated melanomas has response rates of 6% to 15%, with median progression-free survival (PFS) of 2 to 3 months. Until March of 2011, only 2 drugs were approved by the FDA in the United States for metastatic melanoma: interleukin 2 (IL-2) and dacarbazine, which is an alkylating agent. Temozolomide, an orally available congener of dacarbazine, was shown to be noninferior in efficacy in comparison with dacarbazine in a randomized phase III trial. Until now, biochemotherapy and combination chemotherapy based on IL-2 and dacarbazine or temozolomide have not shown statistically significant improvement in overall survival (OS) and cannot be considered standard therapeutic options for metastatic melanoma. In 2011, 2 unique agents were FDA approved for the treatment of metastatic melanoma: ipilimumab and vemurafenib. Ipilimumab, an immunotherapy, and vemurafenib, a BRAF inhibitor, are further discussed in this article ( Figs. 1 and 2 ).
