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https://www.readbyqxmd.com/read/29350548/use-of-helical-tomotherapy-in-locally-advanced-and-or-metastatic-breast-cancer-for-locoregional-treatment
#1
Laura Thery, Alexandre Arsene-Henry, Susan Carroll, Dominique Peurien, Louis Bazire, Magalie Robilliard, Alain Fourquet, Youlia M Kirova
PURPOSE: Helical tomotherapy (HT) is a new promising tool whose use remains to be studied. This work assesses its impact for local irradiation in terms of side effects, as well as tumour control in locally advanced (LABC) and metastatic breast cancer (MBC). METHODS: We retrospectively reviewed data of 66 patients with LABC and MBC. Patients received standard fractionated radiotherapy by HT, with or without concurrent systemic treatment. RESULTS: The median age was 60 years (28-77)...
January 19, 2018: British Journal of Radiology
https://www.readbyqxmd.com/read/29349598/phase-ib-study-evaluating-safety-and-clinical-activity-of-the-anti-her3-antibody-lumretuzumab-combined-with-the-anti-her2-antibody-pertuzumab-and-paclitaxel-in-her3-positive-her2-low-metastatic-breast-cancer
#2
Andreas Schneeweiss, Tjoung-Won Park-Simon, Joan Albanell, Ulrik Lassen, Javier Cortés, Veronique Dieras, Marcus May, Christoph Schindler, Frederik Marmé, Juan Miguel Cejalvo, Maria Martinez-Garcia, Iria Gonzalez, Jose Lopez-Martin, Anja Welt, Christelle Levy, Florence Joly, Francesca Michielin, Wolfgang Jacob, Céline Adessi, Annie Moisan, Georgina Meneses-Lorente, Tomas Racek, Ian James, Maurizio Ceppi, Max Hasmann, Martin Weisser, Andrés Cervantes
Purpose To investigate the safety and clinical activity of comprehensive human epidermal growth factor receptor (HER) family receptor inhibition using lumretuzumab (anti-HER3) and pertuzumab (anti-HER2) in combination with paclitaxel in patients with metastatic breast cancer (MBC). Methods This phase Ib study enrolled 35 MBC patients (first line or higher) with HER3-positive and HER2-low (immunohistochemistry 1+ to 2+ and in-situ hybridization negative) tumors. Patients received lumretuzumab (1000 mg in Cohort 1; 500 mg in Cohorts 2 and 3) plus pertuzumab (840 mg loading dose [LD] followed by 420 mg in Cohorts 1 and 2; 420 mg without LD in Cohort 3) every 3 weeks, plus paclitaxel (80 mg/m2 weekly in all cohorts)...
January 19, 2018: Investigational New Drugs
https://www.readbyqxmd.com/read/29335579/the-effects-of-antibody-engineering-ch-and-cl-in-trastuzumab-and-pertuzumab-recombinant-models-impact-on-antibody-production-and-antigen-binding
#3
Wai-Heng Lua, Wei-Li Ling, Joshua Yi Yeo, Jun-Jie Poh, David Philip Lane, Samuel Ken-En Gan
Current therapeutic antibodies such as Trastuzumab, are typically of the blood circulatory IgG1 class (Cκ/ CHγ1). Due to the binding to Her2 also present on normal cell surfaces, side effects such as cardiac failure can sometimes be associated with such targeted therapy. Using antibody isotype swapping, it may be possible to reduce systemic circulation through increased tissue localization, thereby minimising unwanted side effects. However, the effects of such modifications have yet to be fully characterized, particularly with regards to their biophysical properties in antigen binding...
January 15, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29330210/trastuzumab-plus-pertuzumab-resistance-does-not-preclude-response-to-lapatinib-plus-trastuzumab-in-her2-amplified-colorectal-cancer
#4
Marwan G Fakih
Human epidermal growth factor 2 (HER2) amplification represents a distinct molecular subgroup of colorectal cancers that is associated with anti-epidermal growth factor receptor resistance and sensitivity to dual HER2 targeting. Although clinical trials have reported activity for trastuzumab/pertuzumab and trastuzumab/lapatinib combinations, there are no reports on lapatinib plus trastuzumab activity after resistance to trastuzumab plus pertuzumab. Presented are three cases of HER2 amplified colorectal cancer that developed acquired refractoriness to trastuzumab pertuzumab with subsequent clinical benefit to lapatinib plus trastuzumab, highlighting the potential for HER2 tyrosine kinase inhibition plus trastuzumab in overcoming trastuzumab/pertuzumab resistance...
January 12, 2018: Oncologist
https://www.readbyqxmd.com/read/29326029/neoadjuvant-treatment-with-trastuzumab-and-pertuzumab-plus-palbociclib-and-fulvestrant-in-her2-positive-er-positive-breast-cancer-na-pher2-an-exploratory-open-label-phase-2-study
#5
Luca Gianni, Giancarlo Bisagni, Marco Colleoni, Lucia Del Mastro, Claudio Zamagni, Mauro Mansutti, Milvia Zambetti, Antonio Frassoldati, Raffaella De Fato, Pinuccia Valagussa, Giuseppe Viale
BACKGROUND: In the neoadjuvant setting, blockade of HER2 plus use of an aromatase inhibitor in patients with HER2-positive and oestrogen receptor (ER)-positive breast cancer leads to a pathological complete response in 21% of patients. Convergence of HER2 and ER signals on RB1 suggests that a combined pharmacological intervention directed to these targets could be synergistic. To test this approach, we combined palbociclib to block RB1, fulvestrant to block ER, and trastuzumab with pertuzumab to block HER2 in patients with HER2-positive, ER-positive breast cancer...
January 8, 2018: Lancet Oncology
https://www.readbyqxmd.com/read/29320312/targeted-therapy-for-advanced-solid-tumors-on-the-basis-of-molecular-profiles-results-from-mypathway-an-open-label-phase-iia-multiple-basket-study
#6
John D Hainsworth, Funda Meric-Bernstam, Charles Swanton, Herbert Hurwitz, David R Spigel, Christopher Sweeney, Howard Burris, Ron Bose, Bongin Yoo, Alisha Stein, Mary Beattie, Razelle Kurzrock
Purpose Detection of specific molecular alterations in tumors guides the selection of effective targeted treatment of patients with several types of cancer. These molecular alterations may occur in other tumor types for which the efficacy of targeted therapy remains unclear. The MyPathway study evaluates the efficacy and safety of selected targeted therapies in tumor types that harbor relevant genetic alterations but are outside of current labeling for these treatments. Methods MyPathway ( ClinicalTrials.gov identifier: NCT02091141) is a multicenter, nonrandomized, phase IIa multiple basket study...
January 10, 2018: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/29300831/incidence-and-management-of-diarrhea-in-patients-with-her2-positive-breast-cancer-treated-with-pertuzumab
#7
S M Swain, A Schneeweiss, L Gianni, J J Gao, A Stein, M Waldron-Lynch, S Heeson, M S Beattie, B Yoo, J Cortes, J Baselga
No abstract text is available yet for this article.
January 2, 2018: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29291541/her-2-positive-mucinous-carcinoma-breast-cancer-case-report
#8
Irean Garcia Hernandez, Mauricio Canavati Marcos, Margarita Garza Montemayor, Dulce Lopez Sotomayor, Diana Pineda Ochoa, Gabriela Sofia Gomez Macias
INTRODUCTION: Mucinous carcinoma is a variant of invasive breast carcinomas that accounts for 2% of them and has a better prognosis in contrast to the non-specific invasive carcinoma. They regularly are positive for estrogen and progesterone receptors and, generally, they do not overexpress HER2. When HER2 is positive, the first line treatment is trastuzumab; although the resistance is 52-89% for the non-specific carcinoma, it has been described just once in mucinous carcinoma. CASE SUMMARY: A 48-year-old female presented with a lump in her right breast and after a biopsy, it was diagnosed as mucinous carcinoma in the core biopsy and surgical resection, with positive hormone receptors and HER2 positive (3+) in 100% of the tumor cells...
December 26, 2017: International Journal of Surgery Case Reports
https://www.readbyqxmd.com/read/29287189/human-epidermal-growth-factor-receptor-2-dual-blockade-with-trastuzumab-and-pertuzumab-in-real-life-italian-clinical-practice-versus-the-cleopatra-trial-results
#9
Sabino De Placido, Mario Giuliano, Francesco Schettini, Claudia Von Arx, Giuseppe Buono, Ferdinando Riccardi, Daniela Cianniello, Roberta Caputo, Fabio Puglisi, Marta Bonotto, Alessandra Fabi, Domenico Bilancia, Mariangela Ciccarese, Vito Lorusso, Andrea Michelotti, Dario Bruzzese, Bianca Maria Veneziani, Mariavittoria Locci, Michelino De Laurentiis, Grazia Arpino
OBJECTIVES: Given their inclusion and exclusion criteria, randomized clinical trials (RCT) might not include a population that truly mirrors real life (RL). This raises concerns about the applicability of RCT results in clinical practice. We evaluated the efficacy of anti-HER2 treatment with pertuzumab combined with trastuzumab and a taxane as first-line treatment for HER2-positive metastatic breast cancer in a RL setting, and compared the safety results obtained in our population versus the experimental cohort of the CLEOPATRA RCT, which led to the approval of this therapy...
December 26, 2017: Breast: Official Journal of the European Society of Mastology
https://www.readbyqxmd.com/read/29250202/asco-2017-highlights-in-breast-cancer
#10
REVIEW
Rupert Bartsch, Elisabeth Bergen
At the 2017 ASCO Annual Meeting, several pertinent studies in the field of breast cancer were presented and some are deemed as being potentially practice changing. BrighTNess was the first phase III study to investigate the addition of carboplatin to standard neoadjuvant chemotherapy in triple-negative breast cancer; while toxicity was increased in the experimental group, a significantly higher pathologic complete remission (pCR) rate was observed as well suggesting that adding carboplatin to neoadjuvant anthracycline, cyclophosphamide and taxane-containing regimens is efficacious in otherwise healthy patients...
2017: Memo
https://www.readbyqxmd.com/read/29232309/a-bispecific-antibody-based-on-pertuzumab-fab-has-potent-antitumor-activity
#11
Wentong Deng, Jiayu Liu, Haitao Pan, Li Li, Changhua Zhou, Xiaojuan Wang, Rui Shu, Bin Dong, Donglin Cao, Qing Li, Zhong Wang
Human epidermal growth factor receptor 2 (HER2) is frequently overexpressed and activated in metastatic breast cancers. Monoclonal antibodies targeting Her2, such as trastuzumab and pertuzumab, have become important targeted therapies for patients with HER2-positive breast cancer. Both trastuzumab and pertuzumab can reduce Her2 positive tumor burden by inhibiting Her2 signaling and inducing ADCC activities (antibody dependent cell-mediated cytotoxicity). In this study, we have generated a bispecific antibody, Her2(Per)-S-Fab, by linking the pertuzumab Fab to an anti-CD16 single domain antibody...
January 2018: Journal of Immunotherapy
https://www.readbyqxmd.com/read/29223479/long-term-efficacy-analysis-of-the-randomised-phase-ii-tryphaena-cardiac-safety-study-evaluating-pertuzumab-and-trastuzumab-plus-standard-neoadjuvant-anthracycline-containing-and-anthracycline-free-chemotherapy-regimens-in-patients-with-her2-positive-early
#12
Andreas Schneeweiss, Stephen Chia, Tamas Hickish, Vernon Harvey, Alexandru Eniu, Maeve Waldron-Lynch, Jennifer Eng-Wong, Sarah Kirk, Javier Cortés
BACKGROUND: We report long-term efficacy and cardiac safety outcomes in patients with HER2-positive early breast cancer treated with neoadjuvant pertuzumab plus trastuzumab with anthracycline-containing or anthracycline-free chemotherapy. METHODS: Descriptive efficacy analyses were conducted in patients randomised to group A (cycles 1-6: trastuzumab [8 mg/kg loading dose and 6 mg/kg maintenance] plus pertuzumab [840 mg loading dose and 420 mg maintenance], plus 5-fluorouracil, epirubicin and cyclophosphamide [FEC] [cycles 1-3; 500 mg/m2 5-fluorouracil/100 mg/m2 epirubicin/600 mg/m2 cyclophosphamide] then docetaxel [cycles 4-6; 75 mg/m2, escalated to 100 mg/m2 if well tolerated]), B (cycles 1-3: FEC, cycles 4-6: trastuzumab plus pertuzumab plus docetaxel as mentioned previously) or C (cycles 1-6: trastuzumab plus pertuzumab plus docetaxel [75 mg/m2, without dose escalation], and carboplatin [AUC 6]), five years after randomisation of the last patient...
December 7, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/29209558/development-and-clinical-application-of-anti-her2-monoclonal-and-bispecific-antibodies-for-cancer-treatment
#13
REVIEW
Shengnan Yu, Qian Liu, Xinwei Han, Shuang Qin, Weiheng Zhao, Anping Li, Kongming Wu
HER2-targeted immunotherapy consists of monoclonal antibodies (e.g. trastuzumab, pertuzumab), bispecific antibodies (e.g. MM-111, ertumaxomab) and activated T cells armed with anti-HER2 bispecific antibody (HER2Bi-aATC). Trastuzumab is a classic drug for the treatment of HER2 positive metastatic breast cancer. The combined application of pertuzumab, trastuzumab and paclitaxel has been suggested as a standard therapy for HER2 positive advanced breast cancer. The resistance to anti-HER2 antibody has resulted in disease progression...
2017: Experimental Hematology & Oncology
https://www.readbyqxmd.com/read/29189161/toxicology-of-trastuzumab-an-insight-into-mechanisms-of-cardiotoxicity
#14
Jie An, M Saeed Sheikh
Trastuzumab is a humanized monoclonal antibody that is approved for the treatment of breast and gastric malignancies. Although it has shown promise as a biotherapeutic, its cardiotoxicity remains a major concern. Genotoxic anticancer anthracyclines such as doxorubicin and epirubicin are also known for their cardiotoxic effects. However, trastuzumab and anthracyclines are suggested to mediate cardiotoxicity via different pathways. The available lines of evidence suggest that trastuzumab can exacerbate the cardiotoxic effects of anthracyclines and thus, prior exposure to anthracyclines is a regarded as one of the risk factors for trastuzumab-induced cardiotoxcity...
November 29, 2017: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/29183167/adding-pertuzumab-to-trastuzumab-and-taxanes-in-her2-positive-breast-cancer
#15
Jack Patrick Gleeson, Niamh M Keegan, Patrick G Morris
The monoclonal antibody trastuzumab has improved the median disease free and overall survival of patients with early stage breast cancer that overexpresses the human epidermal growth factor receptor 2 (HER2). Despite this advance, some patients experience cancer relapse and novel approaches are always needed. One such advance is the monoclonal antibody pertuzumab, which prevents dimerisation between members of the HER family of transmembrane glycoprotein receptors. Areas covered: In this review, the authors analyse recent research which has focused on the development of new HER2 targeting agents for HER2-positive breast cancer, particularly pertuzumab, and its addition to trastuzumab and taxanes...
December 3, 2017: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/29182361/ado-trastuzumab-emtansine-t-dm1-in-her2-advanced-breast-cancer-patients-does-pretreatment-with-pertuzumab-matter
#16
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/29181152/impact-of-assay-temperature-on-antibody-binding-characteristics-in-living-cells-a-case-study
#17
João Crispim Encarnação, Pavel Barta, Torgny Fornstedt, Karl Andersson
Kinetic and thermodynamic studies of ligand-receptor interactions are essential for increasing the understanding of receptor activation mechanisms and drug behavior. The characterization of molecular interactions on living cells in real-time goes beyond most current binding assays, and provides valuable information about the dynamics and underlying mechanism of the molecules in a living system. The effect of temperature on interactions in cell-based assays is, however, rarely discussed. In the present study, the effect of temperature on binding of monoclonal antibodies, cetuximab and pertuzumab to specific receptors on living cancer cells was evaluated, and the affinity and kinetics of the interactions were estimated at selected key temperatures...
November 2017: Biomedical Reports
https://www.readbyqxmd.com/read/29181007/interplay-between-natural-killer-cells-and-anti-her2-antibodies-perspectives-for-breast-cancer-immunotherapy
#18
REVIEW
Aura Muntasell, Mariona Cabo, Sonia Servitja, Ignasi Tusquets, María Martínez-García, Ana Rovira, Federico Rojo, Joan Albanell, Miguel López-Botet
Overexpression of the human epidermal growth factor receptor 2 (HER2) defines a subgroup of breast tumors with aggressive behavior. The addition of HER2-targeted antibodies (i.e., trastuzumab, pertuzumab) to chemotherapy significantly improves relapse-free and overall survival in patients with early-stage and advanced disease. Nonetheless, considerable proportions of patients develop resistance to treatment, highlighting the need for additional and co-adjuvant therapeutic strategies. HER2-specific antibodies can trigger natural killer (NK) cell-mediated antibody-dependent cellular cytotoxicity and indirectly enhance the development of tumor-specific T cell immunity; both mechanisms contributing to their antitumor efficacy in preclinical models...
2017: Frontiers in Immunology
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
#19
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
#20
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
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