title: Upcoming strategies for the treatment of metastatic melanoma.
abstract: Prognosis for advanced and metastatic melanoma is poor, with a 5-year survival of 78, 59 and 40% for patients with stage IIIA, IIIB and IIIC, respectively, and a 1-year survival of 62% for M1a, 53% for M1b and 33% for M1c. The unsatisfactory results of actual standard therapies for metastatic melanoma highlight the need for effective new therapeutic strategies. Several drugs, including BRAF, KIT and MEK inhibitors, are currently being evaluated after promising data from Phase I and Phase II studies; Vemurafenib, a BRAF-inhibitor agent, has been approved by the Food and Drug Administration (FDA) for the treatment of patients with unresectable or metastatic melanoma with the BRAF V600E mutation after a significant impact on both progression-free and overall survival was demonstrated compared with dacarbazine in a Phase III trial. Ipilimumab, an immunotherapeutic drug, has proven to be capable of inducing long-lasting responses and was approved for patients with advanced melanoma in first- and second-line treatment by the FDA and in second-line treatment by the European Medicines Agency. Furthermore, a significant survival benefit of the combination of ipilimumab with dacarbazine compared with dacarbazine alone for first-line treatment was reported. In the near future, patients with BRAF mutations could have the chance to benefit from treatment with BRAF inhibitors; patients harboring BRAF or NRAS mutations could be treated with MEK inhibitors; finally, the subgroup of patients with acral, mucosal or chronic sun-damaged melanoma harboring a KIT mutation could benefit from KIT inhibitors. Ipilimumab could become a standard treatment for metastatic melanoma, both as a single agent and in combination; its efficacy has been proven, and researchers should now address their efforts to understanding the predictive variables of response to treatment.
authors.affiliation: Plastic and Reconstructive Surgery, IRCCS Azienda Ospedaliera Universitaria San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy. francesco.spagnolo85@gmail.com
authors.forename: Francesco
authors.initials: F
authors.lastname: Spagnolo
authors.forename: Paola
authors.initials: P
authors.lastname: Queirolo
mesh_terms: D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D003606:Dacarbazine / Q000627:therapeutic use; D006801:Humans; D007211:Indoles / Q000627:therapeutic use; D000074324:Ipilimumab; D020930:MAP Kinase Kinase Kinases / Q000037:antagonists & inhibitors; D008545:Melanoma / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary; D009362:Neoplasm Metastasis; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D048493:Proto-Oncogene Proteins B-raf / Q000037:antagonists & inhibitors; D019009:Proto-Oncogene Proteins c-kit / Q000037:antagonists & inhibitors; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D013449:Sulfonamides / Q000627:therapeutic use; D000077484:Vemurafenib
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D007211:Indoles; D000074324:Ipilimumab; D047428:Protein Kinase Inhibitors; D013449:Sulfonamides; D000077484:Vemurafenib; D003606:Dacarbazine; D019009:Proto-Oncogene Proteins c-kit; D048493:Proto-Oncogene Proteins B-raf; D020930:MAP Kinase Kinase Kinases