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Integrating New Therapies in the Treatment of Advanced Melanoma

  • Skin Cancer (WH Sharfman, Section Editor)
  • Published:
Current Treatment Options in Oncology Aims and scope Submit manuscript

Opinion statement

Treatments for advanced melanoma have evolved rapidly based on improved understanding of the pathways that determine T-cell responses and knowledge of growth-related mutations, which can be targeted with new classes of pharmacologic agents. The FDA approved ipilimumab and vemurafenib for advanced melanoma in 2011. Our practice is to evaluate all tumors from patients with metastatic disease for the presence of a BRAF mutation (Fig. 1). More than 20 years of follow-up show that responders to IL-2 can be cured of their melanoma. Therefore, we recommend high-dose IL-2 as first line therapy for patients with excellent functional status and normal cardiopulmonary reserve regardless of their BRAF mutation status. We use ipilimumab, which can induce durable tumor regressions and improved survival, as initial therapy for patients who refuse or are not candidates for IL-2, also regardless of their BRAF mutation status. Ipilimumab can be used as salvage therapy for patients with advanced disease after IL-2 or vemurafenib. Targeted therapies such as vemurafenib or imatinib can be offered to patients whose melanomas express the BRAF V600E or C-Kit mutations. Vemurafenib is particularly useful for patients whose disease is progressing rapidly, as clinical improvement can be obtained within days of starting therapy and response rates may be as high as 70 %. The major reason we do not recommend vemurafenib as first line treatment in all patients whose tumors have BRAF mutations is the short median duration of response of approximately 7 months. Enrollment in a clinical trial should always be considered for patients with metastatic melanoma. The clinical trial focus has changed from finding any agent with activity in melanoma, to overcoming mechanisms of resistance and enhancing the immunomodulatory activity of these new agents that confer therapeutic benefit. Selected patients can benefit from surgical resection or radiation to manage oligometastatic disease.

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Disclosure

B.D.C.: Consultancy for Bristol-Myers Squibb and Prometheus Pharmaceuticals, payment for development of educational presentations from Prometheus Pharmaceutical and Genentech, travel/accommodations expenses covered or reimbursed from Bristol-Myers Squibb and Prometheus Pharmaceutical. W.J.U: board membership to SAIC-Frederick, National Cancer Institute, and Bristol-Myers Squibb, consultancy for Bristol-Myers Squibb, honoraria from Bristol-Myers Squibb, travel/accommodations expenses covered or reimbursed from Bristol-Myers Squibb, National Cancer Institute, and SAIC-Frederick.

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  1. Providence Cancer Center, 4805 NE Glisan St, Ste 2N35, Portland, OR, 97213, USA

    Brendan D. Curti MD & Walter J. Urba MD, PhD

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  1. Brendan D. Curti MD
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  2. Walter J. Urba MD, PhD
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Correspondence to Brendan D. Curti MD.

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Curti, B.D., Urba, W.J. Integrating New Therapies in the Treatment of Advanced Melanoma. Curr. Treat. Options in Oncol. 13, 327–339 (2012). https://doi.org/10.1007/s11864-012-0201-9

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