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https://www.readbyqxmd.com/read/29129088/systemic-therapy-for-esophagogastric-cancer-targeted-therapies
#1
Tomas G Lyons, Geoffrey Y Ku
The poor prognosis for patients with esophagogastric cancers (EGC) has resulted in an increased focus on the use of targeted agents in this disease. Targets include epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF), Her2, mammalian target of rapamycin (mTOR), MET, poly (ADP-ribose) polymerase (PARP) and claudin 18.2 (CLDN18.2). Trastuzumab, an anti-Her2 antibody, was approved by the U.S. FDA in 2010 as first-line therapy in combination with chemotherapy for Her2-positive disease...
October 2017: Chinese Clinical Oncology
https://www.readbyqxmd.com/read/29112701/effect-of-docetaxel-duration-on-clinical-outcomes-exploratory-analysis-of-cleopatra-a-phase-iii-randomized-controlled-trial
#2
D Miles, Y-H Im, A Fung, B Yoo, A Knott, S Heeson, M S Beattie, S M Swain
Background: Combination pertuzumab, trastuzumab, and docetaxel (D) is considered standard first-line treatment for human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC). This post hoc, exploratory analysis of CLEOPATRA study data evaluated the clinical effects of D treatment duration within this regimen. The clinical benefits of pertuzumab and trastuzumab by different durations of D treatment were also evaluated. Patients and methods: Patients with HER2-positive MBC received trastuzumab and D plus pertuzumab or placebo...
November 3, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29108432/efficacy-and-safety-of-a-combination-of-her2-targeted-agents-as-first-line-treatment-for-metastatic-her2-positive-breast-cancer-a-network-meta-analysis
#3
Henry W C Leung, John-Hang Leung, Agnes L F Chan
BACKGROUND: Using network meta-analysis, we assessed the efficacy and safety of a combination regimen of HER2-targeted agents as first-line treatment for metastatic HER2-positive breast cancer. METHODS: We searched the Medline, Embase, and Cochrane Library electronic databases (through December 2016) for phase II/III randomized controlled trials that compared regimens of one or two HER2-targeted agents combined with trastuzumab or chemotherapy. A network meta-analysis including direct and indirect analyses was conducted in WinBUGS using fixed and random effects...
November 6, 2017: Expert Opinion on Drug Safety
https://www.readbyqxmd.com/read/29078212/-current-status-of-targeted-treatment-in-breast-cancer
#4
Katharina Seiffert, Barbara Schmalfeldt, Volkmar Müller
Within the last years, significant improvements have been achieved in breast cancer treatment, particularly with the development of targeted therapies. Major progress has been made in identifying the drivers malignant growth in oestrogen-receptor-positive breast cancer and the mechanisms of resistance to endocrine therapy. This progress has translated into several targeted therapies that enhance the efficacy of endocrine therapy; inhibitors of the cyclin-dependent kinases CDK4 and CDK6 like palbociclib and inhibitors of mTOR substantially improve progression-free survival...
November 2017: Deutsche Medizinische Wochenschrift
https://www.readbyqxmd.com/read/29067280/charcot-marie-tooth-hereditary-neuropathy-revealed-after-administration-of-docetaxel-in-advanced-breast-cancer
#5
Hampig Raphael Kourie, Nicolas Mavroudakis, Philippe Aftimos, Martine Piccart
Charcot-Marie-Tooth (CMT) neuropathy is the most common hereditary cause of neuropathy. Diagnosis is usually not made during the childhood but in adolescence or late adulthood. It is reported in the literature that some neurotoxic chemotherapeutical agents can reveal an asymptomatic CMT IA hereditary neuropathy. To our knowledge, we report here the first case of CMT IA revealed in a 55-year-old woman after the administration of docetaxel/trastuzumab/pertuzumab for metastatic breast cancer. This case stresses again the necessity to obtain a complete personal and familial anamnesis and to perform a neurologic examination before the administration of neurotoxic chemotherapeutical agents to prevent the clinical expression of these hereditary neuropathies...
October 10, 2017: World Journal of Clinical Oncology
https://www.readbyqxmd.com/read/29059433/an-erbb1-3-neutralizing-antibody-mixture-with-high-activity-against-drug-resistant-her2-breast-cancers-with-erbb-ligand-overexpression
#6
Luis J Schwarz, Katherine E Hutchinson, Brent N Rexer, Mónica Valeria Estrada, Paula I Gonzalez Ericsson, Melinda E Sanders, Teresa C Dugger, Luigi Formisano, Angel Guerrero-Zotano, Monica Red-Brewer, Christian D Young, Johan Lantto, Mikkel W Pedersen, Michael Kragh, Ivan D Horak, Carlos L Arteaga
Background: Plasticity of the ERBB receptor network has been suggested to cause acquired resistance to anti-human epidermal growth factor receptor 2 (HER2) therapies. Thus, we studied whether a novel approach using an ERBB1-3-neutralizing antibody mixture can block these compensatory mechanisms of resistance. Methods: HER2+ cell lines and xenografts (n ≥ 6 mice per group) were treated with the ERBB1-3 antibody mixture Pan-HER, trastuzumab/lapatinib (TL), trastuzumab/pertuzumab (TP), or T-DM1...
November 1, 2017: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/29027290/pertuzumab-and-trastuzumab-infusion-related-cytokine-release-syndrome-in-a-chemotherapy-naive-patient-with-metastatic-breast-cancer
#7
Adonice Khoury, Vikas Parihar, Lillie O'steen, Kartikeya Cherabuddi
Pertuzumab is a monoclonal antibody that targets and down regulates HER-2/neu expression in ductal breast tumors. Other HER-2/neu monoclonal antibodies, particularly trastuzumab, have been implicated to induce infusion related reactions such as cytokine release syndrome (CRS). Here, we report a case of pertuzumab associated CRS prior to infusion of trastuzumab which warranted hospitalization for symptom management.
October 13, 2017: Breast Journal
https://www.readbyqxmd.com/read/28985927/association-between-targeted-her-2-therapy-and-breast-reconstruction-outcomes-a%C3%A2-propensity-score-matched-analysis
#8
Ronnie L Shammas, Eugenia H Cho, Adam D Glener, Luke P Poveromo, Lily R Mundy, Rachel A Greenup, Kimberly L Blackwell, Scott T Hollenbeck
BACKGROUND: Current treatment for HER-2+ breast cancer includes chemotherapy and targeted HER-2 therapy with trastuzumab and/or pertuzumab. Evidence is lacking on the safety of breast reconstructive operations in these patients. We hypothesized that targeted HER-2 therapy was not associated with post-mastectomy reconstructive outcomes. STUDY DESIGN: Women receiving chemotherapy and post-mastectomy reconstruction at Duke University Medical Center from 2006 to 2016 were retrospectively identified...
September 26, 2017: Journal of the American College of Surgeons
https://www.readbyqxmd.com/read/28984651/new-anti-her2-agents-from-second-generation-tyrosine-kinases-inhibitors-to-bifunctional-antibodies
#9
Joseph Gligorov, Sandrine Richard, Vladimir Todorovic
PURPOSE OF REVIEW: HER2-positive breast cancers have benefited since the end of the twentieth century, not only from the improvement of biological knowledge, but also from major technological advances. The latter allowed the synthesis of the first generation of enzymatic inhibitors of the HER receptor family such as lapatinib, but above all, monoclonal antibodies such as trastuzumab or pertuzumab having profoundly modified the management of these cancers. However, despite outstanding progresses, there are still patients who are not cured with these first-generation treatments, and they will need new approaches to improve disease control and impact patients' survival...
November 2017: Current Opinion in Oncology
https://www.readbyqxmd.com/read/28983766/hersintuzumab-a-novel-humanized-anti-her2-monoclonal-antibody-induces-potent-tumor-growth-inhibition
#10
Mohammad Mehdi Amiri, Forough Golsaz-Shirazi, Tahereh Soltantoyeh, Reza Hosseini-Ghatar, Tannaz Bahadori, Jalal Khoshnoodi, Shadi Sadat Navabi, Samira Farid, Mohammad Hossein Karimi-Jafari, Mahmood Jeddi-Tehrani, Fazel Shokri
Humanized monoclonal antibodies (mAbs) against HER2 including trastuzumab and pertuzumab are widely used to treat HER2 overexpressing metastatic breast cancers. These two mAbs recognize distinct epitopes on HER2 and their combination induces a more potent blockade of HER2 signaling than trastuzumab alone. Recently, we have reported characterization of a new chimeric mAb (c-1T0) which binds to an epitope different from that recognized by trastuzumab and significantly inhibits proliferation of HER2 overexpressing tumor cells...
October 6, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/28982879/using-tils-to-predict-therapeutic-effect-of-chemotherapy-pertuzumab-trastuzumab-docetaxel-on-her2-positive-breast-cancer
#11
Shinichiro Kashiwagi, Yuka Asano, Wataru Goto, Koji Takada, Katsuyuki Takahashi, Takaharu Hatano, Tsutomu Takashima, Shuhei Tomita, Hisashi Motomura, Masahiko Ohsawa, Kosei Hirakawa, Masaichi Ohira
BACKGROUND/AIM: Recently, reports of the clinical implications of tumor-infiltrating lymphocytes (TILs) in breast cancer treatment have increased. We evaluated that chemotherapy with a TPD regimen (trastuzumab, pertuzumab, docetaxel) against HER2-positive breast cancer, using TILs as indicators. PATIENTS AND METHODS: The subjects were 24 patients who had received TPD-chemotherapy. A semi-quantitative evaluation of lymphocytes invading the stroma in needle biopsy specimens prior to treatment as TILs was conducted, after which, sensitivity to chemotherapy and patient prognosis were evaluated...
October 2017: Anticancer Research
https://www.readbyqxmd.com/read/28973704/neoadjuvant-and-adjuvant-therapies-for-breast-cancer
#12
REVIEW
Susmitha Apuri
Breast cancer remains the most common cancer in women in the United States, the second most common cause of cancer death, and the main cause of death in women ages 45 to 55 years. Molecular analyses have shown that breast cancer is divided into several subtypes (luminal A, luminal B, human epidermal growth factor receptor 2 [HER2] enriched, and basal-like), based on microarray techniques. Patients diagnosed as having breast cancer may undergo adjuvant or neoadjuvant chemotherapy, depending on the tumor size, hormone receptor, HER2/neu status, and desire for breast preservation...
October 2017: Southern Medical Journal
https://www.readbyqxmd.com/read/28965422/cost-effectiveness-of-pertuzumab-combined-with-trastuzumab-and-docetaxel-as-a-first-line-treatment-for-her-2-positive-metastatic-breast-cancer
#13
Henry W C Leung, Agnes L F Chan, Chih-Hsin Muo, John Hang Leung
OBJECTIVE: To provide perspective for the National Health Insurance Bureau (NHIB), we determined the cost-effectiveness of pertuzumab combined with trastuzumab and docetaxel (TDP) versus trastuzumab and docetaxel (TD) as a first-line treatment for HER-2 positive metastatic breast cancer. METHODS: We used a Markov model to simulate cost-effectiveness, disease progression, and survival, based on clinical data and transition probabilities extracted from the CLEOPATRA study...
October 10, 2017: Expert Review of Pharmacoeconomics & Outcomes Research
https://www.readbyqxmd.com/read/28959366/mode-of-action-of-pertuzumab-in-combination-with-trastuzumab-plus-docetaxel-therapy-in-a-her2-positive-breast-cancer-xenograft-model
#14
Yoriko Yamashita-Kashima, Sei Shu, Keigo Yorozu, Yoichiro Moriya, Naoki Harada
In a Phase III trial for HER2-positive breast cancer (the CLEOPATRA study), the triple-drug combination arm of pertuzumab plus trastuzumab plus docetaxel showed significantly longer progression-free survival and overall survival than did the trastuzumab plus docetaxel arm. In this study, we investigated the mechanism of action of the triple-drug combination therapy in vivo. For this purpose, we established a mouse xenograft model using KPL-4, a HER2-positive human breast cancer cell line, in which the triple-drug combination treatment dramatically induced tumor regression compared with double-drug combinations (trastuzumab plus docetaxel, pertuzumab plus docetaxel, or pertuzumab plus trastuzumab)...
October 2017: Oncology Letters
https://www.readbyqxmd.com/read/28945833/de-escalation-strategies-in-her2-positive-early-breast-cancer-ebc-final-analysis-of-the-wsg-adapt-her2-hr-phase-ii-trial-efficacy-safety-and-predictive-markers-for-12%C3%A2-weeks-of-neoadjuvant-dual-blockade-with-trastuzumab-and-pertuzumab-%C3%A2-weekly-paclitaxel
#15
U A Nitz, O Gluz, M Christgen, E-M Grischke, D Augustin, S Kuemmel, M Braun, J Potenberg, A Kohls, K Krauss, A Stefek, C Schumacher, H Forstbauer, T Reimer, H Fischer, C Liedtke, R Wuerstlein, J Schumacher, R Kates, H Kreipe, N Harbeck
Background: Response rates in HER2-overexpressing EBC treated with neoadjuvant chemotherapy and trastuzumab (T) have been improved by addition of pertuzumab (P). The prospective, phase II, neoadjuvant WSG-ADAPT HER2+/HR- trial assessed whether patients with strong early response to dual blockade alone might achieve pathological complete response (pCR) comparable to that of patients receiving dual blockade and chemotherapy. Patients and methods: Female patients with HER2+/HR- EBC (M0) were randomized (5:2) to 12 weeks of T + P ± weekly paclitaxel (pac) at 80 mg/m2...
November 1, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28945315/quantitating-adcc-against-adherent-cells-impedance-based-detection-is-superior-to-release-membrane-permeability-or-caspase-activation-assays-in-resolving-antibody-dose-response
#16
Gábor Tóth, János Szöllősi, György Vereb
Monoclonal antibody-based immunotherapeutics will dominate Pharma's next generation of blockbuster drugs, and Fc-associated functions, including antibody dependent cellular cytotoxicity (ADCC) are among the highly desired activities mediated by these antibodies. Therefore, quantitative evaluation of ADCC is required during drug development. Our objective was to find the most suitable and reliable nonradioactive method for quantitative analysis of in vitro ADCC against adherent cells, which often serve as models for solid tumors...
September 25, 2017: Cytometry. Part A: the Journal of the International Society for Analytical Cytology
https://www.readbyqxmd.com/read/28939847/dual-mab-her-family-blockade-in-head-and-neck-cancer-human-cell-lines-combined-with-photon-therapy
#17
Jean-Baptiste Guy, Benoîte Méry, Edouard Ollier, Sophie Espenel, Alexis Vallard, Anne-Sophie Wozny, Stéphanie Simonet, Alexandra Lauret, Priscillia Battiston-Montagne, Dominique Ardail, Gersende Alphonse, Chloé Rancoule, Claire Rodriguez-Lafrasse, Nicolas Magné
Head and neck cancer stem cells (CSCs) are highly resistant to treatment. When EGFR is overexpressed in head and neck squamous cell carcinoma (HNSCC), HER2 and HER3 are also expressed. The aim of the present study was to investigate the effect of HER1/2/3 blockade through a combination of cetuximab and pertuzumab, with or without photon irradiation, on the proliferation and migration/invasion capabilities of an HNSCC chemo- and radioresistant human cell line (SQ20B) and its corresponding stem cell subpopulation...
September 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28919583/polyclonal-antibody-against-different-extracellular-subdomains-of-her2-induces-tumor-growth-inhibition-in-vitro
#18
Reza Hosseini Ghatar, Tahereh Soltantoyeh, Motahareh Bahadori, Jalal Khoshnoodi, Forough Golsaz Shirazi, Mahmood Jeddi Tehrani, Mohammad Mehdi Amiri, Fazel Shokri
BACKGROUND: Human epidermal growth factor receptor 2 (HER2) has a crucial role in several malignancies. The extracellular domain of HER2 (HER2-ECD) has been extensively employed as an important target in passive and active immunotherapy. Isolated recombinant prokaryotic HER2-ECD subdomains were previously found to be ineffective in inducing anti-tumor antibody response. OBJECTIVE: To employ recombinant eukaryotic HER2-ECD subdomains to raise anti-HER2 antibodies and determine their anti-tumor activity in vitro...
September 2017: Iranian Journal of Immunology: IJI
https://www.readbyqxmd.com/read/28915642/a-retrospective-multicentric-observational-study-of-trastuzumab-emtansine-in-her2-positive-metastatic-breast-cancer-a-real-world-experience
#19
Patrizia Vici, Laura Pizzuti, Andrea Michelotti, Isabella Sperduti, Clara Natoli, Lucia Mentuccia, Luigi Di Lauro, Domenico Sergi, Paolo Marchetti, Daniele Santini, Emanuela Magnolfi, Laura Iezzi, Luca Moscetti, Agnese Fabbri, Alessandra Cassano, Antonino Grassadonia, Claudia Omarini, Federico Piacentini, Andrea Botticelli, Ilaria Bertolini, Angelo Fedele Scinto, Germano Zampa, Maria Mauri, Loretta D'Onofrio, Valentina Sini, Maddalena Barba, Marcello Maugeri-Saccà, Ernesto Rossi, Elisabetta Landucci, Silverio Tomao, Antonio Maria Alberti, Francesco Giotta, Corrado Ficorella, Vincenzo Adamo, Antonio Russo, Vito Lorusso, Katia Cannita, Sandro Barni, Lucio Laudadio, Filippo Greco, Ornella Garrone, Marina Della Giulia, Paolo Marolla, Giuseppe Sanguineti, Barbara Di Cocco, Gennaro Ciliberto, Ruggero De Maria, Teresa Gamucci
We addressed trastuzumab emtansine (T-DM1) efficacy in HER2+ metastatic breast cancer patients treated in real-world practice, and its activity in pertuzumab-pretreated patients. We conducted a retrospective, observational study involving 23 cancer centres, and 250 patients. Survival data were analyzed by Kaplan Meier curves and log rank test. Factors testing significant in univariate analysis were tested in multivariate models. Median follow-up was 15 months and median T-DM1 treatment-length 4 months. Response rate was 41...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28881627/structural-basis-of-a-novel-heterodimeric-fc-for-bispecific-antibody-production
#20
Hudie Wei, Haiyan Cai, Yuhao Jin, Pilin Wang, Qingqing Zhang, Yihui Lin, Weixiao Wang, Jinke Cheng, Naiyan Zeng, Ting Xu, Aiwu Zhou
Bispecific antibodies provide an efficient tool for combinational clinical therapy. Here we have engineered a heterodimeric Fc for bispecific antibodies production by combining the knob-into-hole and electrostatic steering strategies where a bulky hydrophobic residue Phe405 of the IgG CH3 interface is mutated to a charged residue Lys and Lys409 of the corresponding CH3 domain is mutated to Ala. The crystal structure of this Fc heterodimer solved here at 2.7Å resolution revealed how these two mutations resulted a complementary binding interface and explained why F405K mutation could effectively inhibit Fc homodimer formation during protein expression...
August 1, 2017: Oncotarget
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