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Management of metastatic melanoma: improved survival in a national cohort following the approvals of checkpoint blockade immunotherapies and targeted therapies.

ABSTRACT: BACKGROUND:Immune checkpoint blockade (ICB) and BRAFV600-targeted therapy have demonstrated substantial clinical efficacy for patients with stage 4 melanoma in clinical trials; however, their impact on survival and barriers to treatment in the "real-life" setting remains unknown. METHODS:Patients who presented with cutaneous melanoma during 2004-2015 using the National Cancer Database, which comprises?>?70% of all newly diagnosed cancers in the U.S., were evaluated for predictors of presenting with stage 4 disease and receiving ICB, and for their associated unadjusted and risk-adjusted overall survival (OS). RESULTS:17,975 patients presented with stage 4 metastatic cutaneous melanoma. Overall, patients who presented after the FDA's initial approvals (starting in 2011) for ICB and BRAFV600-targeted therapy demonstrated a 31% relative improvement in 4-year OS (p?

SUBMITTER: Dobry AS

PROVIDER: S-EPMC6249064 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

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Management of metastatic melanoma: improved survival in a national cohort following the approvals of checkpoint blockade immunotherapies and targeted therapies.

Dobry Allison S AS Zogg Cheryl K CK Hodi F Stephen FS Smith Timothy R TR Ott Patrick A PA Iorgulescu J Bryan JB

Cancer immunology, immunotherapy : CII 20180906 12

<h4>Background</h4>Immune checkpoint blockade (ICB) and BRAF<sup>V600</sup>-targeted therapy have demonstrated substantial clinical efficacy for patients with stage 4 melanoma in clinical trials; however, their impact on survival and barriers to treatment in the "real-life" setting remains unknown.<h4>Methods</h4>Patients who presented with cutaneous melanoma during 2004-2015 using the National Cancer Database, which comprises > 70% of all newly diagnosed cancers in the U.S., were evaluated for ...[more]

PMID: 30191256

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Project description:BackgroundThe development of brain metastases is common for systemic treatment failure in patients with melanoma and has been associated with a poor prognosis. Recent advances with BRAF and immune checkpoint therapies have led to improved patient survival. Herein, the authors evaluated the risk of de novo brain metastases and survival among patients with melanoma brain metastases (MBM) since the introduction of more effective therapies.MethodsPatients with unresectable AJCC stage III/IV melanoma who received first-line systemic therapy at Moffitt Cancer Center between 2000 and 2012 were identified. Data were collected regarding patient characteristics, stage of disease, systemic therapies, MBM status/management, and overall survival (OS). The risk of de novo MBM was calculated using a generalized estimating equation model and survival comparisons were performed using Kaplan-Meier and Cox proportional analyses.ResultsA total of 610 patients were included, 243 of whom were diagnosed with MBM (40%). Patients with MBM were younger, with a lower frequency of regional metastasis. No significant differences were noted with regard to sex, BRAF status, or therapeutic class. The risk of de novo MBM was found to be similar among patients treated with chemotherapy, biochemotherapy, BRAF-targeted therapy, ipilimumab, and anti-programmed cell death protein 1/programmed death-ligand 1 regimens. The median OS of patients with MBM was significantly shorter when determined from the time of first regional/distant metastasis but not when determined from the time of first systemic therapy. The median OS from the time of MBM diagnosis was 7.5 months, 8.5 months, and 22.7 months, respectively, for patients diagnosed from 2000 to 2008, 2009 to 2010, and 2011 to the time of last follow-up (P = .002).ConclusionsBrain metastases remain a common source of systemic treatment failure. The OS for patients with MBM has improved significantly. Further research into MBM prevention is needed. Cancer 2018;124:297-305. © 2017 American Cancer Society.

Dataset Information

Management of metastatic melanoma: improved survival in a national cohort following the approvals of checkpoint blockade immunotherapies and targeted therapies.

Publications

Management of metastatic melanoma: improved survival in a national cohort following the approvals of checkpoint blockade immunotherapies and targeted therapies.

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