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Neratinib for metastasic breast cancer

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https://www.readbyqxmd.com/read/27078022/neratinib-plus-paclitaxel-vs-trastuzumab-plus-paclitaxel-in-previously-untreated-metastatic-erbb2-positive-breast-cancer-the-nefert-t-randomized-clinical-trial
#1
Ahmad Awada, Ramon Colomer, Kenichi Inoue, Igor Bondarenko, Rajendra A Badwe, Georgia Demetriou, Soo-Chin Lee, Ajay O Mehta, Sung-Bae Kim, Thomas Bachelot, Chanchal Goswami, Suryanarayan Deo, Ron Bose, Alvin Wong, Feng Xu, Bin Yao, Richard Bryce, Lisa A Carey
Importance: Efficacious ERBB2 (formerly HER2 or HER2/neu)-directed treatments, in addition to trastuzumab and lapatinib, are needed. Objective: To determine whether neratinib, an irreversible pan-ERBB tyrosine kinase inhibitor, plus paclitaxel improves progression-free survival compared with trastuzumab plus paclitaxel in the first-line treatment of recurrent and/or metastatic ERBB2-positive breast cancer. Design, Setting, and Participants: In the randomized, controlled, open-label NEfERT-T trial conducted from August 2009 to December 2014 at 188 centers in 34 countries in Europe, Asia, Africa, and North America, 479 women with previously untreated recurrent and/or metastatic ERBB2-positive breast cancer were randomized to 1 of 2 treatment arms (neratinib-paclitaxel [n = 242] or trastuzumab-paclitaxel [n = 237])...
December 1, 2016: JAMA Oncology
https://www.readbyqxmd.com/read/26834058/translational-breast-cancer-research-consortium-tbcrc-022-a-phase-ii-trial-of-neratinib-for-patients-with-human-epidermal-growth-factor-receptor-2-positive-breast-cancer-and-brain-metastases
#2
MULTICENTER STUDY
Rachel A Freedman, Rebecca S Gelman, Jeffrey S Wefel, Michelle E Melisko, Kenneth R Hess, Roisin M Connolly, Catherine H Van Poznak, Polly A Niravath, Shannon L Puhalla, Nuhad Ibrahim, Kimberly L Blackwell, Beverly Moy, Christina Herold, Minetta C Liu, Alarice Lowe, Nathalie Y R Agar, Nicole Ryabin, Sarah Farooq, Elizabeth Lawler, Mothaffar F Rimawi, Ian E Krop, Antonio C Wolff, Eric P Winer, Nancy U Lin
PURPOSE: Evidence-based treatments for metastatic, human epidermal growth factor receptor 2 (HER2)-positive breast cancer in the CNS are limited. Neratinib is an irreversible inhibitor of erbB1, HER2, and erbB4, with promising activity in HER2-positive breast cancer; however, its activity in the CNS is unknown. We evaluated the efficacy of treatment with neratinib in patients with HER2-positive breast cancer brain metastases in a multicenter, phase II open-label trial. PATIENTS AND METHODS: Eligible patients were those with HER2-positive brain metastases (≥ 1 cm in longest dimension) who experienced progression in the CNS after one or more line of CNS-directed therapy, such as whole-brain radiotherapy, stereotactic radiosurgery, and/or surgical resection...
March 20, 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/25285186/therapeutic-considerations-in-treating-her2-positive-metastatic-breast-cancer
#3
Ciara C O'Sullivan, Karen L Smith
Despite advances in detection and treatment, metastatic breast cancer (MBC) remains the second highest cause of cancer-related death for women in the United States. Human epidermal growth factor receptor-2 (HER2) is amplified in 25-30% of breast cancers and is associated with aggressive disease and, historically, with poorer outcomes. The advent of trastuzumab, a monoclonal antibody to HER2, revolutionized the management of HER2-positive breast cancer (BC) in the metastatic and adjuvant settings. However, relapse despite adjuvant trastuzumab and resistance to trastuzumab in the metastatic setting remain substantial clinical problems for many patients with HER2-positive BC...
September 1, 2014: Current Breast Cancer Reports
https://www.readbyqxmd.com/read/24787047/new-protein-kinase-inhibitors-in-breast-cancer-afatinib-and-neratinib
#4
Xiaosong Zhang, Pamela N Munster
INTRODUCTION: Human epidermal growth factor receptor (HER) 2 is overexpressed in 20 - 25% of breast cancers, and has historically been a poor prognostic marker. The introduction of trastuzumab, the first fully humanized monoclonal antibody targeting HER2, has drastically changed the outcomes of metastatic breast cancers. However, despite initial response, most patients develop resistance. Recent data suggest that strategies targeting more than one member of HER family may circumvent trastuzumab resistance and confer synergistic effects...
June 2014: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/20176546/-management-of-metastatic-her2-positive-breast-cancer-present-and-future
#5
REVIEW
S Guiu, B Coudert, L Favier, L Arnould, P Fumoleau
HER2-positive breast cancer accounts for 20 to 25% of breast cancers. The surexpression of this tyrosine-kinase receptor is often associated with a poor prognosis. However, the management and the outcome of these patients have changed these last ten years with trastuzumab. Despite the encouraging results obtained with this humanized monoclonal antibody directed against the HER2-receptor, used alone or in association with chemotherapy in metastatic patients, progression under trastuzumab are usually observed and resistances to this treatment are described...
March 2010: Bulletin du Cancer
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