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Aim: To describe treatment changes from 2011 to 2017 and demographic/clinical characteristics of patients with advanced melanoma who received systemic therapy by BRAF status. Patients & methods: Treatment patterns were evaluated in adults from the Oncology Services Comprehensive Electronic Records database who received antimelanoma systemic therapy. Results: Checkpoint inhibitors were prevailingly prescribed (66%); usage increased from 2011 (21%) to 2017 (84%). BRAF/MEK inhibitors were the second most common (21%); usage increased from 2011 (6%) to 2012 (18%) and stabilized until 2017 (22%). BRAF/MEK inhibitors (65%) and checkpoint inhibitors (57%) were predominantly used for BRAFMut melanoma. Conclusion: Overall, checkpoint inhibitors have supplanted other therapies for advanced melanoma. Treatment shifts have occurred for BRAFMut melanoma, notably increased use of checkpoint inhibitors and BRAF/MEK combinations compared with monotherapies.

Background: The poor response to chemotherapy and the brief response to vemurafenib in metastatic melanoma patients, make the identification of new therapeutic approaches an urgent need. Interestingly the increased expression and activity of the Aurora kinase B during melanoma progression suggests it as a promising therapeutic target. Methods: The efficacy of the Aurora B kinase inhibitor barasertib-HQPA was evaluated in BRAF mutated cells, sensitive and made resistant to vemurafenib after chronic exposure to the drug, and in BRAF wild type cells. The drug effectiveness has been evaluated as cell growth inhibition, cell cycle progression and cell migration. In addition, cellular effectors of drug resistance and response were investigated. Results: The characterization of the effectors responsible for the resistance to vemurafenib evidenced the increased expression of MITF or the activation of Erk1/2 and p-38 kinases in the newly established cell lines with a phenotype resistant to vemurafenib. The sensitivity of cells to barasertib-HQPA was irrespective of BRAF mutational status. Barasertib-HQPA induced the mitotic catastrophe, ultimately causing apoptosis and necrosis of cells, inhibited cell migration and strongly affected the glycolytic metabolism of cells inducing the release of lactate. In association i) with vemurafenib the gain in effectiveness was found only in BRAF(V600K) cells while ii) with nab-paclitaxel, the combination was more effective than each drug alone in all cells. Conclusions: These findings suggest barasertib as a new therapeutic agent and as enhancer of chemotherapy in metastatic melanoma treatment. [ABSTRACT FROM AUTHOR]

Aim: To describe treatment changes from 2011 to 2017 and demographic/clinical characteristics of patients with advanced melanoma who received systemic therapy by BRAF status., Patients & Methods: Treatment patterns were evaluated in adults from the Oncology Services Comprehensive Electronic Records database who received antimelanoma systemic therapy., Results: Checkpoint inhibitors were prevailingly prescribed (66%); usage increased from 2011 (21%) to 2017 (84%). BRAF/MEK inhibitors were the second most common (21%); usage increased from 2011 (6%) to 2012 (18%) and stabilized until 2017 (22%). BRAF/MEK inhibitors (65%) and checkpoint inhibitors (57%) were predominantly used for BRAF Mut melanoma., Conclusion: Overall, checkpoint inhibitors have supplanted other therapies for advanced melanoma. Treatment shifts have occurred for BRAF Mut melanoma, notably increased use of checkpoint inhibitors and BRAF/MEK combinations compared with monotherapies., Competing Interests: Financial & competing interests disclosure S Shah, L Raskin and D Cohan are employees of and stockholders in Amgen Inc. O Hamid has served as a consultant for Amgen Inc., Novartis, Roche, Bristol-Meyers Squibb, Merck; has served on speakers bureaus for Amgen Inc., Bristol-Meyers Squibb, Genentech, Novartis, Array, and Sanofi-Regeneron; and has received institutional research funding from AstraZeneca, Bristol-Meyers Squibb, Celldex, Genentech Roche, Immunocore, Incyte, Merck, Merck Serono, MedImmune, Novartis, Pfizer, Amgen Inc., Cytomx, Iovance, Regeneron, and Polynoma. M Freeman has served as an advisory board consultant for Bristol-Meyers Squibb, Merck, Novartis, and Sanofi-Regeneron. The study was funded by Amgen Inc. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. Medical writing support was provided by M Johnson (Complete Healthcare Communications, LLC, PA, USA) and was funded by Amgen Inc., (© 2019 Amgen Inc.)