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

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      New England Journal of Medicine
      Massachusetts Medical Society

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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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            Combination nivolumab and ipilimumab or nivolumab alone in melanoma brain metastases: a multicentre randomised phase 2 study

            Nivolumab monotherapy and combination nivolumab plus ipilimumab increase proportions of patients achieving a response and survival versus ipilimumab in patients with metastatic melanoma; however, efficacy in active brain metastases is unknown. We aimed to establish the efficacy and safety of nivolumab alone or in combination with ipilimumab in patients with active melanoma brain metastases.
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              Is Open Access

              Combining Immune Checkpoint Inhibitors: Established and Emerging Targets and Strategies to Improve Outcomes in Melanoma

              The immune system employs several checkpoint pathways to regulate responses, maintain homeostasis and prevent self-reactivity and autoimmunity. Tumor cells can hijack these protective mechanisms to enable immune escape, cancer survival and proliferation. Blocking antibodies, designed to interfere with checkpoint molecules CTLA-4 and PD-1/PD-L1 and counteract these immune suppressive mechanisms, have shown significant success in promoting immune responses against cancer and can result in tumor regression in many patients. While inhibitors to CTLA-4 and the PD-1/PD-L1 axis are well-established for the clinical management of melanoma, many patients do not respond or develop resistance to these interventions. Concerted efforts have focused on combinations of approved therapies aiming to further augment positive outcomes and survival. While CTLA-4 and PD-1 are the most-extensively researched targets, results from pre-clinical studies and clinical trials indicate that novel agents, specific for checkpoints such as A2AR, LAG-3, IDO and others, may further contribute to the improvement of patient outcomes, most likely in combinations with anti-CTLA-4 or anti-PD-1 blockade. This review discusses the rationale for, and results to date of, the development of inhibitory immune checkpoint blockade combination therapies in melanoma. The clinical potential of new pipeline therapeutics, and possible future therapy design and directions that hold promise to significantly improve clinical prognosis compared with monotherapy, are discussed.
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                Author and article information

                Journal
                New England Journal of Medicine
                N Engl J Med
                Massachusetts Medical Society
                0028-4793
                1533-4406
                September 27 2019
                September 27 2019
                Affiliations
                [1 ]From the Royal Marsden NHS Foundation Trust, London (J.L.), and the College of Medicine, Swansea University, Swansea (J.W.) — both in the United Kingdom; the Oncology Institute of Veneto IRCCS, Padua (V.C.-S.), the European Institute of Oncology, IRCCS, Milan (P.F.F.), Istituto Nazionale Tumori IRCCS Fondazione Pascale, Naples (P.A.A.), the Immunotherapy and Somatic Cell Therapy Unit, IRCCS Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori, Meldola (M.G.), and the Center for Immuno...
                Article
                10.1056/NEJMoa1910836
                31562797
                d1087853-680f-43e2-b20d-7674054126f6
                © 2019

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