Melanoma Treatment (PDQ®): Treatment - Health Professional Information [NCI] - Treatment Option Overview
Although melanoma that has spread to distant sites is rarely curable, both ipilimumab and vemurafenib have demonstrated an improvement in progression-free survival (PFS) and OS in international, multicenter, randomized trials in patients with unresectable or advanced disease, resulting in U.S. Food and Drug Administration (FDA) approval in 2011. These single agents are rarely curative; however, clinical trials that incorporate these agents are testing combinations in an attempt to prevent development of drug resistance. Vemurafenib is a selective BRAF V600E kinase inhibitor, and its indication is limited to patients with a demonstrated BRAF V600E mutation by an FDA-approved test. Clinical trials are testing targeted therapies in the smaller patient subsets (e.g., those with mutations in NRAS, c-KIT, CDK4, GNAQ or GNA11). Information about ongoing clinical trials is available from the NCI Web site.
Interleukin-2 (IL-2) was approved by the FDA in 1998 on the basis of durable complete response (CR) rates in a minority of patients (0% –8%) with previously treated metastatic melanoma in eight phase I and II studies. No improvement in OS has been demonstrated in randomized trials.
Dacarbazine (DTIC) was approved in 1970 based on overall response rates. Phase III trials indicate an overall response rate of 10% to 20%, with rare CRs observed. An impact on OS has not been demonstrated in randomized trials.[12,13,14,15,16] Temozolomide, an oral alkylating agent, appeared to be similar to DTIC (intravenous administration) in a randomized phase III trial with a primary endpoint of OS; however, the trial was designed for superiority, and the sample size was inadequate to prove equivalency.
Patients with all stages of melanoma may be considered candidates for ongoing clinical trials. Information about ongoing clinical trials is available from the NCI Web site.
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