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Emtansine

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https://www.readbyqxmd.com/read/29326401/efficacy-and-tolerability-of-trastuzumab-emtansine-in-advanced-human-epidermal-growth-factor-receptor-2-positive-breast-cancer
#1
W Yeo, M Y Luk, I S Soong, T Ys Yuen, T Y Ng, F Kf Mo, K Chan, S Y Wong, J Tsang, C Leung, J Js Suen, R Kc Ngan
INTRODUCTION: The management of human epidermal growth factor receptor 2 (HER2)-positive breast cancer has changed dramatically with the introduction and widespread use of HER2-targeted therapies. There is, however, relatively limited real-world information about the effectiveness and safety of trastuzumab emtansine (T-DM1) in the Hong Kong Chinese patients. We assessed the efficacy and toxicity profiles among local patients with HER2-positive advanced breast cancer who had received T-DM1 therapy in the second-line setting and beyond...
January 12, 2018: Hong Kong Medical Journal, Xianggang Yi Xue za Zhi
https://www.readbyqxmd.com/read/29313813/a-phase-ii-study-of-trastuzumab-emtansine-in-her2-positive-non-small-cell-lung-cancer
#2
Katsuyuki Hotta, Keisuke Aoe, Toshiyuki Kozuki, Kadoaki Ohashi, Kiichiro Ninomiya, Eiki Ichihara, Toshio Kubo, Takashi Ninomiya, Kenichi Chikamori, Daijiro Harada, Naoyuki Nogami, Taizo Hirata, Shiro Hinotsu, Shinichi Toyooka, Katsuyuki Kiura
Trastuzumab emtansine (T-DM1), an anti-HER2 antibody-drug conjugate, has been shown to significantly improve survival in HER2-positive breast cancer. We report a phase II trial of T-DM1 monotherapy in relapsed non-small-cell lung cancer (NSCLC). with documented HER2-positivity (immunohistochemistry [IHC] 3+, both IHC 2+ and fluorescence in situ hybridization [FISH] +, or exon 20 mutation). This study was terminated early due to limited efficacy. The demographic characteristics in the 15 assessable patients were as follows: age (median: 67 years), sex (male: 47%), performance status (0-1: 80%), and HER2 status (IHC 3+: 33%; IHC 2+/FISH: 20%; mutation: 47%)...
December 4, 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/29274446/a-progressively-enlarging-cerebellar-hematoma-concurrent-with-t-dm1-treatment-case-report
#3
Marcelo D Vilela, William T Longstreth, Hugo As Pedrosa, Gabriel Ob Gil, Juliano M Duarte, Marco Antonio D Filho
BACKGROUND: Trastuzumab emtansine, an antibody-drug conjugate commonly abbreviated as T-DM1, is accepted as an effective therapy for trastuzumab-resistant metastatic HER2-positive breast cancer. T-DM1 significantly increases progression-free and overall survival when compared to lapatinib plus capecitabine in patients with HER2-positive breast cancer previously treated with trastuzumab and a taxane. Among the common side effects related to T-DM1, thrombocytopenia and mucosal hemorrhage are seen, although they are infrequently judged to be clinically significant...
December 20, 2017: World Neurosurgery
https://www.readbyqxmd.com/read/29239690/antibody-drug-conjugates-design-and-development-for-therapy-and-imaging-in-and-beyond-cancer-labex-mabimprove-industrial-workshop-july-27-28-2017-tours-france
#4
Camille Martin, Claire Kizlik-Masson, André Pèlegrin, Hervé Watier, Marie-Claude Viaud-Massuard, Nicolas Joubert
The annual "Antibody Industrial Symposium", co organized by LabEx MAbImprove, MabDesign and Polepharma, was held in Tours, France on June 27-28, 2017. The focus was on antibody-drug-conjugates (ADCs), new entities which realize the hope of Paul Ehrlich's magic bullet. ADCs result from the bioconjugation of a highly cytotoxic drug to a selective monoclonal antibody, which acts as a vector. Building on knowledge gained during the development of three approved ADCs, brentuximab vedotin (Adcetris®), ado trastuzumab emtansine (Kadcyla®) and inotuzumab ozogamicin (Besponsa®), and the many ADCs in development, this meeting addressed strategies and the latest innovations in the field from fundamental research to manufacturing...
December 14, 2017: MAbs
https://www.readbyqxmd.com/read/29231164/lapatinib-plus-capecitabine-in-patients-with-her2-positive-metastatic-breast-cancer-a%C3%A2-systematic-review%C3%A2
#5
Rebecca Madden, Sam Kosari, Gregory M Peterson, Nasser Bagheri, Jackson Thomas
OBJECTIVE: Human epidermal growth factor receptor 2 (HER2)-positive breast cancer, which accounts for 20 - 25% of cases of breast cancers, is highly aggressive. Due to cardiotoxicity and increasing resistance associated with trastuzumab, the first-line treatment, there is a need for effective second-line therapies in treating HER2-positive breast cancer. In this context, there has been increasing interest in the combination of lapatinib plus capecitabine. The aim of this systematic review was to assess the efficacy of lapatinib plus capecitabine for HER2-positive breast cancer after progression with trastuzumab therapy, in comparison with capecitabine monotherapy and other agents such as vinorelbine and trastuzumab emtansine...
December 12, 2017: International Journal of Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/29217763/improved-tumor-penetration-and-single-cell-targeting-of-antibody-drug-conjugates-increases-anticancer-efficacy-and-host-survival
#6
Cornelius Cilliers, Bruna Menezes, Ian Nessler, Jennifer Linderman, Greg Thurber
Current antibody-drug conjugates (ADC) have made advances in engineering the antibody, linker, conjugation site, small molecule payload and drug-to-antibody ratio (DAR). However, the relationship between heterogeneous intratumoral distribution and efficacy of ADC is poorly understood. Here we compared trastuzumab and ado-trastuzumab emtansine (T-DM1) to study the impact of ADC tumor distribution on efficacy. In a mouse xenograft model insensitive to trastuzumab, co-administration of trastuzumab with a fixed dose of T-DM1 at 3:1 and 8:1 ratios dramatically improved ADC tumor penetration and resulted in twice the improvement in median survival compared to T-DM1 alone...
December 7, 2017: Cancer Research
https://www.readbyqxmd.com/read/29214842/trastuzumab-emtansine-determining-its-role-in-management-of-her2-breast-cancer
#7
Deborah B Doroshow, Patricia M LoRusso
Trastuzumab emtansine is an antibody-drug conjugate comprised of the anti-HER2 monoclonal antibody trastuzumab linked to DM1 (emtansine), a potent cytotoxic maytansinoid derivative, by a stable linker. This structure results in improved tumor-directed cytotoxicity in HER2+ breast cancer with reduced systemic toxicities, particularly the cardiac toxicities associated with single agent trastuzumab. Phase III trials have demonstrated improved progression-free and overall survival in heavily pretreated patients with advanced HER2+ breast cancer, with an acceptable toxicity profile...
December 7, 2017: Future Oncology
https://www.readbyqxmd.com/read/29202823/trastuzumab-emtansine-delays-and-overcomes-resistance-to-the-third-generation-egfr-tki-osimertinib-in-nsclc-egfr-mutated-cell-lines
#8
Silvia La Monica, Daniele Cretella, Mara Bonelli, Claudia Fumarola, Andrea Cavazzoni, Graziana Digiacomo, Lisa Flammini, Elisabetta Barocelli, Roberta Minari, Nadia Naldi, Pier Giorgio Petronini, Marcello Tiseo, Roberta Alfieri
BACKGROUND: Osimertinib is a third-generation EGFR-TKI with a high selective potency against T790M-mutant NSCLC patients. Considering that osimertinib can lead to enhanced HER-2 expression on cell surface and HER-2 overexpression is a mechanism of resistance to osimertinib, this study was addressed to investigate the potential of combining osimertinib with trastuzumab emtansine (T-DM1) in order to improve the efficacy of osimertinib and delay or overcome resistance in NSCLC cell lines with EGFR activating mutation and with T790M mutation or HER-2 amplification...
December 4, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/29189914/correction-to-population-pharmacokinetics-of-trastuzumab-emtansine-in-previously-treated-patients-with-her2-positive-advanced-gastric-cancer-agc
#9
Shang-Chiung Chen, Matts Kagedal, Yuying Gao, Bei Wang, Marie-Laurence Harle-Yge, Sandhya Girish, Jin Jin, Chunze Li
The online version of the original article can be.
November 30, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/29188435/antibody-drug-conjugates-pharmacokinetic-pharmacodynamic-modeling-preclinical-characterization-clinical-studies-and-lessons-learned
#10
REVIEW
William D Hedrich, Tamer E Fandy, Hossam M Ashour, Hongbing Wang, Hazem E Hassan
Antibody-drug conjugates are an emerging class of biopharmaceuticals changing the landscape of targeted chemotherapy. These conjugates combine the target specificity of monoclonal antibodies with the anti-cancer activity of small-molecule therapeutics. Several antibody-drug conjugates have received approval for the treatment of various types of cancer including gemtuzumab ozogamicin (Mylotarg®), brentuximab vedotin (Adcetris®), trastuzumab emtansine (Kadcyla®), and inotuzumab ozogamicin, which recently received approval (Besponsa®)...
November 29, 2017: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/29182361/ado-trastuzumab-emtansine-t-dm1-in-her2-advanced-breast-cancer-patients-does-pretreatment-with-pertuzumab-matter
#11
Alessandra Fabi, Diana Giannarelli, Luca Moscetti, Daniele Santini, Alberto Zambelli, Michelino De Laurentiis, Michele Caruso, Daniele Generali, Enrichetta Valle, Vita Leonardi, Katia Cannita, Grazia Arpino, Gianfranco Filippelli, Gianluigi Ferretti, Marianna Giampaglia, Filippo Montemurro, Cecilia Nisticò, Simona Gasparro, Francesco Cognetti
AIM: We evaluated the outcomes of patients treated with ado-trastuzumab emantasine (T-DM1) after first-line pertuzumab/trastuzumab, compared with those receiving a trastuzumab-only-based regimen. PATIENTS & METHODS: Patients who received second-line T-DM1 after pertuzumab/trastuzumab (n = 34) were compared with those who received only trastuzumab (n = 73). RESULTS: Overall response rate was 33.3% in patients with prior pertuzumab and 57...
November 28, 2017: Future Oncology
https://www.readbyqxmd.com/read/29180848/safety-and-efficacy-of-the-addition-of-pertuzumab-to-t-dm1-%C3%A2-taxane-in-patients-with-her2-positive-locally-advanced-or-metastatic-breast-cancer-a-pooled-analysis
#12
REVIEW
Jing Zhang, Jinying Li, Chenjing Zhu, Yanlin Song, Fan Xia, Xuelei Ma
Background: The aim of this review was to systematically evaluate the safety and efficacy of the addition of pertuzumab to trastuzumab emtansine (T-DM1) ± taxane in patients with human epidermal growth factor receptor 2 (HER2)-positive, locally advanced breast cancer (LABC) or metastatic breast cancer (MBC). Materials and methods: Several databases were searched for relevant clinical trials. The study characteristics, details of adverse events (AEs) and details of treatment efficacy were extracted for analysis...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/29175149/neoadjuvant-trastuzumab-pertuzumab-and-chemotherapy-versus-trastuzumab-emtansine-plus-pertuzumab-in-patients-with-her2-positive-breast-cancer-kristine-a-randomised-open-label-multicentre-phase-3-trial
#13
Sara A Hurvitz, Miguel Martin, W Fraser Symmans, Kyung Hae Jung, Chiun-Sheng Huang, Alastair M Thompson, Nadia Harbeck, Vicente Valero, Daniil Stroyakovskiy, Hans Wildiers, Mario Campone, Jean-François Boileau, Matthias W Beckmann, Karen Afenjar, Rodrigo Fresco, Hans-Joachim Helms, Jin Xu, Yvonne G Lin, Joseph Sparano, Dennis Slamon
BACKGROUND: HER2-targeted treatments have improved outcomes in patients with HER2-positive breast cancer in the neoadjuvant, adjuvant, and metastatic settings; however, some patients remain at risk of relapse or death for many years after treatment of early-stage disease. Therefore, new strategies are needed. We did a phase 3 trial to assess a neoadjuvant regimen for HER2-positive breast cancer that replaces traditional systemic chemotherapy with targeted treatment. METHODS: We did a randomised, open-label phase 3 KRISTINE trial in 68 Translational Research In Oncology centres (hospitals and specialty cancer centres in Asia, Europe, USA, and Canada)...
November 23, 2017: Lancet Oncology
https://www.readbyqxmd.com/read/29156892/trastuzumab-emtansine-in-her2-positive-metastatic-breast-cancer-what-is-the-best-sequence
#14
EDITORIAL
Francesco Ricci, Christophe Le Tourneau
No abstract text is available yet for this article.
November 6, 2017: Chinese Clinical Oncology
https://www.readbyqxmd.com/read/29116596/antibody-drug-conjugates-for-the-treatment-of-solid-tumors-clinical-experience-and-latest-developments
#15
Aiko Nagayama, Leif W Ellisen, Bruce Chabner, Aditya Bardia
Antibody-drug conjugates (ADCs) are complex immunoconjugates designed to selectively deliver toxic small molecules preferentially to cancer cells. These immunoconjugates consist of a monoclonal antibody - directed to a tumor antigen - and a cytotoxic agent that is conjugated to the antibody via a molecular linker. Following the binding to a specific antigen on the surface of cancer cells, the conjugate is internalized and releases its cytotoxic payload to kill the malignant cell. ADCs that have gained regulatory approval from the US Food and Drug Administration (FDA) include brentuximab vedotin for CD30-positive Hodgkin's lymphoma and trastuzumab emtansine for human epidermal growth factor receptor 2 (HER2)-positive breast cancer...
November 8, 2017: Targeted Oncology
https://www.readbyqxmd.com/read/29069935/trastuzumab-modified-dm1-loaded-nanoparticles-for-her2-breast-cancer-treatment-an-in-vitro-and-in-vivo-study
#16
Ling Rong, Shuping Zhou, Xinkuang Liu, Amin Li, Tao Jing, Xueke Liu, Yinci Zhang, Shiyu Cai, Xiaolong Tang
BACKGROUND: Emtansine (DM1) is a highly potent anti-microtubule agent that has shown promising results for breast cancer treatment, but side effects limit its widespread clinical use. In this research, a new nano-drug was developed to integrate DM1 agent with antibody targeting. METHODS: A system of novel nanoparticles (NPs) DM1-NPs-trastuzumab (DM1-NPs-Tmab) of DM1 combined with (anti-HER2 antibody, Herceptin®, Trastuzumab) was developed for HER2(+) breast cancer treatment, and its physical characterization and antitumor biological activity were investigated...
October 25, 2017: Artificial Cells, Nanomedicine, and Biotechnology
https://www.readbyqxmd.com/read/29054985/caveolae-mediated-endocytosis-as-a-novel-mechanism-of-resistance-to-trastuzumab-emtansine-t-dm1
#17
Matthew Sung, Xingzhi Tan, Bingwen Lu, Jonathan Golas, Christine Hosselet, Fang Wang, Laurie Tylaska, Lindsay King, Dahui Zhou, Russell Dushin, Jeremy S Myers, Edward Rosfjord, Judy Lucas, Hans-Peter Gerber, Frank Loganzo
Trastuzumab emtansine (T-DM1) is an antibody-drug conjugate (ADC) that has demonstrated clinical benefit for patients with HER2+ metastatic breast cancer, however its clinical activity is limited by inherent or acquired drug resistance. The molecular mechanisms that drive clinical resistance to T-DM1, especially in HER2+ tumors, are not well understood. We used HER2+ cell lines to develop models of T-DM1 resistance utilizing a cyclical dosing schema in which cells received T-DM1 in an "on-off" routine until a T-DM1 resistant population was generated...
October 20, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/29043411/population-pharmacokinetics-of-trastuzumab-emtansine-in-previously-treated-patients-with-her2-positive-advanced-gastric-cancer-agc
#18
Shang-Chiung Chen, Matts Kagedal, Yuying Gao, Bei Wang, Marie-Laurence Harle-Yge, Sandhya Girish, Jin Jin, Chunze Li
PURPOSE: Ado-trastuzumab emtansine (T-DM1) is an antibody-drug conjugate comprising trastuzumab conjugated via a stable thioether linker to DM1, a highly potent cytotoxic agent. A population pharmacokinetics (PK) analysis was performed to characterize T-DM1 PK and evaluate the impact of patient characteristics on T-DM1 PK in previously treated patients with HER2-positive advanced gastric cancer (AGC). METHODS: Following T-DM1 weekly or every three weeks dosing, T-DM1 concentration measurements (n = 780) were collected from 136 patients in the GATSBY (NCT01641939) study and analyzed using nonlinear mixed effects modeling...
October 17, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/29022084/exposure-response-analyses-of-trastuzumab-emtansine-in-patients-with-her2-positive-advanced-breast-cancer-previously-treated-with-trastuzumab-and-a-taxane
#19
Chunze Li, Bei Wang, Shang-Chiung Chen, Russell Wada, Dan Lu, Xin Wang, Daniel Polhamus, Jonathan French, Shweta Vadhavkar, Alexander Strasak, Melanie Smitt, Amita Joshi, Meghna Samant, Angelica Quartino, Jin Jin, Sandhya Girish
PURPOSE: In the phase III EMILIA study, trastuzumab emtansine (T-DM1) significantly improved progression-free survival (PFS) and overall survival (OS) versus capecitabine plus lapatinib (control) in previously treated human epidermal growth factor receptor 2-positive advanced breast cancer. Using EMILIA data, we evaluated the T-DM1 exposure-response relationship. METHODS: Exposure-response relationships were examined with four exposure metrics [model-predicted and observed minimum concentration (C min) and area under the concentration-time curve from time zero to day 21 of T-DM1 at cycle 1] and multiple efficacy (OS, PFS, objective response rate) and safety (grade ≥ 3 adverse events, grade ≥ 3 thrombocytopenia, grade ≥ 3 hepatotoxicity) endpoints...
December 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28974266/endophilin-a2-promotes-her2-internalization-and-sensitivity-to-trastuzumab-based-therapy-in-her2-positive-breast-cancers
#20
Tomas Baldassarre, Peter Truesdell, Andrew W Craig
BACKGROUND: Human epidermal growth factor receptor-2 (HER2) is amplified and a clinical target in a subset of human breast cancers with high rates of metastasis. Targeted therapies involving the antibody trastuzumab and trastuzumab-emtansine (T-DM1) have greatly improved outcomes for HER2-positive (HER2+) breast cancer patients. However, resistance to these targeted therapies can develop and limit their efficacy. Here, we test the involvement of the endocytic adaptor protein endophilin A2 (Endo II) in HER2+ breast cancer models, and their responses to treatments with trastuzumab and T-DM1...
October 3, 2017: Breast Cancer Research: BCR
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