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Targeted agents and immunotherapies: optimizing outcomes in melanoma.

Treatment options for patients with metastatic melanoma, and especially BRAF-mutant melanoma, have changed dramatically in the past 5 years, with the FDA approval of eight new therapeutic agents. During this period, the treatment paradigm for BRAF-mutant disease has evolved rapidly: the standard-of-care BRAF-targeted approach has shifted from single-agent BRAF inhibition to combination therapy with a...

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Immunomodulating property of MAPK inhibitors: from translational knowledge to clinical implementation.

Treatment of metastatic melanoma was radically changed by the introduction of inhibitors of BRAF, an oncogene mutated in 40-50% of patients. Another area of advancement was the use of immunotherapy, and specifically, immune checkpoint inhibitors. There is compelling evidence that oncogenic BRAF, in addition to driving melanoma proliferation, differentiation and survival, induces T-cell suppression directly...

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Immune checkpoint inhibitors and targeted therapies for metastatic melanoma: A network meta-analysis.

Background Immune checkpoint inhibitors and targeted therapies, two new class of drugs for treatment of metastatic melanoma, have not been compared in randomized controlled trials (RCT). We quantitatively summarized the evidence and compared immune and targeted therapies in terms of both efficacy and toxicity. Methods A comprehensive search for RCTs of immune checkpoint inhibitors and...

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Genomic and Transcriptomic Features of Response to Anti-PD-1 Therapy in Metastatic Melanoma.

PD-1 immune checkpoint blockade provides significant clinical benefits for melanoma patients. We analyzed the somatic mutanomes and transcriptomes of pretreatment melanoma biopsies to identify factors that may influence innate sensitivity or resistance to anti-PD-1 therapy. We find that overall high mutational loads associate with improved survival, and tumors from responding patients are enriched for mutations...

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Factors predictive of response, disease progression, and overall survival after dabrafenib and trametinib combination treatment: a pooled analysis of individual patient data from randomised trials

Background Dabrafenib plus trametinib treatment provides significant benefits over BRAF-inhibitor monotherapy in patients with BRAFV600E-mutant or BRAFV600K-mutant advanced melanoma; however, in many patients the disease progresses, leading to death. With many treatment options available, understanding clinical factors that predict long-term response and survival for treatments is important for optimisation of patient management. We aimed to...

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BRAF inhibition improves tumor recognition by the immune system

In spite of the fact that they occur at high rates, the clinical responses of BRAFV600 mutant metastatic melanoma to BRAF inhibitors are usually short-lasting, with most cases progressing within less than 8 mo. Immunomodulatory strategies initiated after progression have recently been reported to be poorly efficient. By characterizing the immunological interactions between T cells...

Combined nivolumab and ipilimumab versus ipilimumab alone in patients with advanced melanoma: 2-year overall survival outcomes in a multicentre, randomised, controlled, phase 2 trial
Articolo

Combined nivolumab and ipilimumab versus ipilimumab alone in patients with advanced melanoma: 2-year overall survival outcomes in a multicentre, randomised, controlled, phase 2 trial

Summary Background Results from phase 2 and 3 trials in patients with advanced melanoma have shown significantbimprovements in the proportion of patients achieving an objective response and prolonged progression-free survival with the combination of nivolumab (an anti-PD-1 antibody) plus ipilimumab (an anti-CTLA-4 antibody) compared with ipilimumab alone. We report 2-year overall survival data from a...