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      Current Melanoma Treatments: Where Do We Stand?

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          Abstract

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          In this manuscript, we discuss recent updates on melanoma-related clinical trial data. We explore diverse topics, including new therapeutic agents and novel combinations that are being tested in early-phase clinical trials. Furthermore, we review long-term efficacy and safety data from the clinical trials that led to the currently approved drugs in the melanoma landscape. We analyze data from human clinical trials in the metastatic setting, adjuvant setting and neoadjuvant setting. Moreover, we review recent breakthroughs related to the management after resistance, as well as the discovery of new targets. Lastly, we explore clinical trials for non-cutaneous melanoma, such as uveal and mucosal melanoma.

          Abstract

          Groundbreaking research in immunology and cancer biology in the last few decades has led to the discovery and development of novel therapeutics, such as immune checkpoint inhibitors and targeted therapies, which have revolutionized the clinical care of patients with metastatic melanoma. Updated data from the largest clinical trials continue to support the use of these treatment modalities, both in the metastatic and in adjuvant settings, with studies showing the predicted plateau effect on survival curves. However, with growing evidence that neoadjuvant therapy is also associated with high rates of recurrence-free survival, the question about whether patients should receive adjuvant or neoadjuvant treatment raises new questions about therapeutic options. Finally, management after resistance and intervention with novel immunotherapies are newer challenges, particularly in the field of non-cutaneous melanoma.

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          Most cited references41

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          Five-Year Survival with Combined Nivolumab and Ipilimumab in Advanced Melanoma

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            Five-Year Outcomes with Dabrafenib plus Trametinib in Metastatic Melanoma

            Patients who have unresectable or metastatic melanoma with a BRAF V600E or V600K mutation have prolonged progression-free survival and overall survival when receiving treatment with BRAF inhibitors plus MEK inhibitors. However, long-term clinical outcomes in these patients remain undefined. To determine 5-year survival rates and clinical characteristics of the patients with durable benefit, we sought to review long-term data from randomized trials of combination therapy with BRAF and MEK inhibitors.
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              Atezolizumab, vemurafenib, and cobimetinib as first-line treatment for unresectable advanced BRAFV600 mutation-positive melanoma (IMspire150): primary analysis of the randomised, double-blind, placebo-controlled, phase 3 trial

              IMspire150 aimed to evaluate first-line combination treatment with BRAF plus MEK inhibitors and immune checkpoint therapy in BRAFV600 mutation-positive advanced or metastatic melanoma.
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                Author and article information

                Journal
                Cancers (Basel)
                Cancers (Basel)
                cancers
                Cancers
                MDPI
                2072-6694
                09 January 2021
                January 2021
                : 13
                : 2
                : 221
                Affiliations
                [1 ]The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; nina.bhardwaj@ 123456mssm.edu (N.B.); philip.friedlander@ 123456mssm.edu (P.F.)
                [2 ]The Kimberly and Eric J. Waldman Department of Dermatology at Mount Sinai, New York, NY 10029, USA
                [3 ]Department of Dermatology and Allergology, Ludwig-Maximilian University, Geschwister-Scholl-Platz 1, 80539 München, Germany; Lucie.Heinzerling@ 123456med.uni-muenchen.de
                Author notes
                [* ]Correspondence: alvaro.moreira@ 123456mssm.edu
                [†]

                Extra-mural member of the Parker Institute for Cancer Immunotherapy.

                Author information
                https://orcid.org/0000-0001-5718-3643
                Article
                cancers-13-00221
                10.3390/cancers13020221
                7827568
                33435389
                8d3eaace-6e17-437a-8cc5-47e6e11df29c
                © 2021 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 19 November 2020
                : 01 January 2021
                Categories
                Review

                melanoma,clinical trials,metastatic,adjuvant,neoadjuvant,resistance,toxicity

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