keyword
https://read.qxmd.com/read/38540113/charting-the-course-in-sequencing-antibody-drug-conjugates-in-breast-cancer
#1
REVIEW
Giuseppe Saltalamacchia, Rosalba Torrisi, Rita De Sanctis, Giovanna Masci, Chiara Miggiano, Mariangela Gaudio, Chiara Benvenuti, Flavia Jacobs, Riccardo Gerosa, Armando Santoro, Alberto Zambelli
Based on the unprecedented results observed in recent clinical trials, antibody-drug conjugates (ADCs) have revolutionized the treatment algorithm of metastatic breast cancer (mBC). The strategy of sequencing different ADCs in other lines of therapy is highly attractive, but the proportion of patients who have undergone such a strategy in the context of published clinical trials is still limited, especially for modern ADCs. HER2-positive disease is primarily managed with a sequence of different ADCs. Historically, trastuzumab emtansine (T-DM1) has been the most commonly used ADC for both early and metastatic HER2-positive disease...
February 23, 2024: Biomedicines
https://read.qxmd.com/read/38528295/a-real-world-study-of-treatment-sequences-and-second-line-clinical-outcomes-in-patients-with-her2-positive-metastatic-breast-cancer-in-us-community-practice
#2
JOURNAL ARTICLE
Della Varghese, Giovanna I Cruz, Colden Johanson, Liz Toland, Miguel Miranda, Eleanor C Faherty, David Harland, Henry G Kaplan
PURPOSE: Standard-of-care for HER2-positive metastatic breast cancer (HER2 + mBC) patients consists of trastuzumab ± pertuzumab with chemotherapy in first-line (1L), and ado-trastuzumab emtansine (T-DM1) or the more recently approved trastuzumab deruxtecan (T-DXd) in second-line (2L). Contemporary data on treatment sequencing and real-world effectiveness is limited. This study aims to report 2L treatments and outcomes among HER2 + mBC patients in the United States (US)...
March 25, 2024: International Journal of Clinical Oncology
https://read.qxmd.com/read/38523303/recurrent-severe-hypocalcemia-following-chemotherapy-regimen-changes-in-advanced-breast-cancer-two-case-reports
#3
JOURNAL ARTICLE
Yurina Yanase, Hiroko Bando, Riko Sato, Tomohei Matsuo, Aya Ueda, Mai Okazaki, Sachie Hashimoto, Akiko Iguchi-Manaka, Hisato Hara
BACKGROUND: As an oncologic emergency related to abnormalities in calcium metabolism, hypercalcemia associated with paraneoplastic syndrome and bone metastases is well known. Meanwhile, the incidence of hypocalcemia is low, except in cases associated with bone-modifying agents used for bone metastases. Hypocalcemia induced by bone-modifying agents typically occurs early after the initial administration, and its incidence can be significantly reduced by preventive administration of calcium and vitamin D3 supplements...
March 25, 2024: Journal of Medical Case Reports
https://read.qxmd.com/read/38502572/effects-of-trastuzumab-emtansine-on-canine-urothelial-carcinoma-cells-in-vitro-and-in-vivo
#4
JOURNAL ARTICLE
Kosei Sakai, Daiki Kato, Junka Yoshinaka, Yosuke Takahashi, Namiko Ikeda, Susumu Aoki, Takaaki Iguchi, Shingo Ishikawa, Norio Yamagishi, Shunsuke Shimamura, Takayuki Nakagawa
Urothelial carcinoma (UC) is the most common malignancy of the urinary tract in dogs and has aggressive behaviour. Although human epidermal growth factor receptor 2 (HER2) is a known therapeutic target with evidence in canine UC, the efficacy of anti-HER2 antibody drugs remains unknown. This study aimed to investigate the effects of anti-HER2 antibody drugs including trastuzumab and trastuzumab emtansine (T-DM1) on canine UC cell lines in vitro and in vivo. Four canine UC cell lines (Nene, TCCUB, Love, and Sora) were used...
March 19, 2024: Veterinary and Comparative Oncology
https://read.qxmd.com/read/38464505/clinical-outcomes-of-patients-with-her2-positive-metastatic-breast-cancer-to-the-brain-with-first-line-trastuzumab-pertuzumab-and-chemotherapy-in-a-real-world-setting
#5
JOURNAL ARTICLE
Sarah Sharman Moser, Lior Apter, Idit Livnat, Roni Ginsburg, Adva Yarden, Michal Drori, Anat Drizon, Gabriel Chodick, Nava Siegelmann-Danieli
BACKGROUND: In this observational study, we analyzed the treatment patterns and clinical outcomes of patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (mBC) who developed brain metastases during their disease in a 2.7 million-member public health-provider in Israel. METHODS: Newly diagnosed patients with mBC who initiated first-line treatment between January 2013 and June 2021 were identified. Time on treatment (ToT) and overall survival (OS) were assessed at a minimum of 6 months follow-up (cutoff: December 2021)...
2024: Breast Cancer: Targets and Therapy
https://read.qxmd.com/read/38461323/neoadjuvant-adjuvant-pertuzumab-in-her2-positive-early-breast-cancer-final-analysis-of-the-randomized-phase-iii-peony-trial
#6
RANDOMIZED CONTROLLED TRIAL
Liang Huang, Da Pang, Hongjian Yang, Wei Li, Shusen Wang, Shude Cui, Ning Liao, Yongsheng Wang, Chuan Wang, Yuan-Ching Chang, Hwei-Chung Wang, Seok Yun Kang, Jae Hong Seo, Kunwei Shen, Suphawat Laohawiriyakamol, Zefei Jiang, Haiyan Wang, François Lamour, Grace Song, Michelle Curran, Chunzhe Duan, Sanne Lysbet de Haas, Eleonora Restuccia, Zhimin Shao
The randomized, multicenter, double-blind, placebo-controlled, phase III PEONY trial (NCT02586025) demonstrated significantly improved total pathologic complete response (primary endpoint) with dual HER2 blockade in HER2-positive early/locally advanced breast cancer, as previously reported. Here, we present the final, long-term efficacy (secondary endpoints: event-free survival, disease-free survival, overall survival) and safety analysis (62.9 months' median follow-up). Patients (female; n = 329; randomized 2:1) received neoadjuvant pertuzumab/placebo with trastuzumab and docetaxel, followed by adjuvant 5-fluorouracil, epirubicin, and cyclophosphamide, then pertuzumab/placebo with trastuzumab until disease recurrence or unacceptable toxicity, for up to 1 year...
March 9, 2024: Nature Communications
https://read.qxmd.com/read/38453523/evidence-for-cytoprotective-autophagy-in-response-to-her2-targeted-monoclonal-antibodies
#7
JOURNAL ARTICLE
Ahmed M Elshazly, Aya A Elzahed, David A Gewirtz
The advent of HER2-targeted monoclonal antibodies such as trastuzumab has significantly improved the clinical outcomes for patients with breast cancer overexpressing HER2, and more recently also for gastric cancers. However, the development of resistance, as is frequently the case for other antineoplastic modalities, constrains clinical efficacy. Multiple molecular mechanisms and signaling pathways have been investigated for their potential involvement in the development of resistance to HER2-targeted therapies, among which is autophagy...
March 7, 2024: Journal of Pharmacology and Experimental Therapeutics
https://read.qxmd.com/read/38403093/incidence-of-antibody-drug-conjugate-related-fatigue-in-patients-with-breast-cancer-a-systematic-review-and-meta-analysis
#8
REVIEW
Hengheng Zhang, GuoShuang Shen, Ping Yang, Jinming Li, Zitao Li, Zhen Liu, Miaozhou Wang, Fuxing Zhao, Dengfeng Ren, Zhilin Liu, Jiuda Zhao, Yi Zhao
BACKGROUND: Numerous studies have reported the efficacy of antibody-drug conjugates (ADCs) for treating breast cancer. However, during cytotoxic drug treatment, long-term disabling fatigue is common. Moreover, studies in the relevant literature have indicated that fatigue can significantly increase the incidence of depression and sleep disorders. Therefore, this meta-analysis aims to evaluate the incidence of fatigue in breast cancer survivors treated with ADCs. METHODS: PubMed, EMBASE, Web of Science, and Cochrane Library databases were systematically searched for articles and conference abstracts published before March 16, 2023...
February 23, 2024: Critical Reviews in Oncology/hematology
https://read.qxmd.com/read/38398191/next-generation-her2-targeted-antibody-drug-conjugates-in-breast-cancer
#9
REVIEW
Brittney S Zimmerman, Francisco J Esteva
Human epidermal growth factor receptor 2 (HER2) tyrosine kinase is overexpressed in 20% of breast cancers and associated with a less favorable prognosis compared to HER2-negative disease. Patients have traditionally been treated with a combination of chemotherapy and HER2-targeted monoclonal antibodies such as trastuzumab and pertuzumab. The HER2-targeted antibody-drug conjugates (ADCs) trastuzumab emtansine (T-DM1) and trastuzumab deruxtecan (T-DXd) represent a novel class of therapeutics in breast cancer...
February 16, 2024: Cancers
https://read.qxmd.com/read/38393609/addressing-residual-disease-in-her2-positive-and-triple-negative-breast-cancer-what-is-next
#10
REVIEW
Ilana Schlam, Joshua Dower, Filipa Lynce
PURPOSE OF REVIEW: To summarize the treatment strategies for patients with human epidermal growth factor receptor 2 (HER2)-positive disease and triple-negative breast cancer (TNBC) who have residual disease after preoperative systemic therapy. RECENT FINDINGS: There has been a shift towards neoadjuvant systemic therapy for selected patients with HER2-positive and TNBC. Assessing the tumor's response to therapy provides prognostic information and allows individualization of the postoperative treatment for these patients based on the tumor response to neoadjuvant therapy...
February 23, 2024: Current Oncology Reports
https://read.qxmd.com/read/38384285/a-pharmacovigilance-study-on-antibody-drug-conjugate-adc-related-neurotoxicity-based-on-the-fda-adverse-event-reporting-system-faers
#11
JOURNAL ARTICLE
Linlin Tang, Cuicui Sun, Wenshan Liu, Haiyan Wu, Chuanhua Ding
Background: Antibody-drug conjugates (ADCs) are a relatively new class of anticancer agents that use monoclonal antibodies to specifically recognize tumour cell surface antigens. However, off-target effects may lead to severe adverse events. This study evaluated the neurotoxicity of ADCs using the FDA Adverse Event Reporting System (FAERS) database. Research design and methods: Data were extracted from the FAERS database for 2004 Q1 to 2022 Q4. We analysed the clinical characteristics of ADC-related neurological adverse events (AEs)...
2024: Frontiers in Pharmacology
https://read.qxmd.com/read/38367127/comparison-of-trastuzumab-emtansine-trastuzumab-deruxtecan-and-disitamab-vedotin-in-a-multiresistant-her2-positive-breast-cancer-lung-metastasis-model
#12
JOURNAL ARTICLE
Negar Pourjamal, Narjes Yazdi, Aleksi Halme, Vadim Le Joncour, Pirjo Laakkonen, Pipsa Saharinen, Heikki Joensuu, Mark Barok
Human epidermal growth factor 2 (HER2)-positive breast cancer with lung metastases resistant to targeted agents is a common therapeutic challenge. Absence of preclinical lung metastasis models that are resistant to multiple anti-HER2 targeted drugs hampers the development of novel therapies. We established a novel HER2-positive breast cancer cell line (L-JIMT-1) with a high propensity to form lung metastases from the parenteral JIMT-1 cell line by injecting JIMT-1 cells into immunodeficient SCID mice. Lung metastases developed in all mice injected with L-JIMT-1 cells, and more rapidly and in greater numbers compared with the parental JIMT-1 cells...
February 17, 2024: Clinical & Experimental Metastasis
https://read.qxmd.com/read/38363526/estimating-public-economic-gains-from-early-breast-cancer-and-curative-treatment-a-case-study-in-human-epidermal-growth-factor-receptor-her-2-positive-targeted-therapies
#13
JOURNAL ARTICLE
Svenn Alexander Kommandantvold, Nikos Kotsopoulos, Isabel Monteiro, Ana Ladeiras, Andrew Hogan, Felipe Barboza Magalhães de Araujo, Mark P Connolly
INTRODUCTION: Cancer diagnosis influences the choices that patients make regarding current and future labor market activity. These choices have implications for governments based on resulting changes in taxes paid and benefits received. In this analysis we explore how human growth receptor 2 (HER2)-positive residual invasive breast cancer and different treatments influence government accounts excluding health costs. METHODS: HER2-positive early breast cancer (eBC) health states from a published disease model were used to establish likelihood of working and wage impact at different stages of disease...
February 16, 2024: Oncology and Therapy
https://read.qxmd.com/read/38360912/antibody-and-antibody-fragments-site-specific-conjugation-using-new-q-tag-substrate-of-bacterial-transglutaminase
#14
JOURNAL ARTICLE
Meddy El Alaoui, Eva Sivado, Anne-Catherine Jallas, Lamia Mebarki, Michael R Dyson, Franck Perrez, Sandrine Valsesia-Wittmann, Said El Alaoui
During the last few years Antibody-Drug Conjugates (ADCs) have become one of the most active and very promising therapeutic weapons. Lessons learned from the traditional chemical conjugations (via lysine or cysteine residues of the antibodies) and the clinical studies of the developed ADCs have recently paved the way to the improvement of the conjugation technologies. Use of site-specific conjugation is considered as the promising path for improving the design and development of homogeneous ADCs with controlled Drug-Antibody ratio (DAR)...
February 15, 2024: Cell Death Discovery
https://read.qxmd.com/read/38327983/comparing-the-difference-of-adverse-events-with-her2-inhibitors-a-study-of-the-fda-adverse-event-reporting-system-faers
#15
JOURNAL ARTICLE
Yiwen Bao, Jiaju Chen, Luting Duan, Fujue Wang, Han Lai, Zeming Mo, Weiliang Zhu
Aim and background: This study attempted to identify similarities and differences in adverse events (AEs) between human epidermal growth factor receptor 2 (HER2) inhibitors, especially those related to hemorrhagic events and nervous system disorders. Methods: This study summarized the types, frequencies, and system organ classes (SOCs) of AEs of HER2 inhibitors. The US Food and Drug Administration Adverse Event Reporting System (FAERS) data from January 2004 through March 2022 was collected and analyzed. Disproportionality analyses were conducted to detect AEs signals for every HER2 inhibitor...
2024: Frontiers in Pharmacology
https://read.qxmd.com/read/38319231/targeting-tacc3-induces-immunogenic-cell-death-and-enhances-t-dm1-response-in-her2-positive-breast-cancer
#16
JOURNAL ARTICLE
Mustafa Emre Gedik, Ozge Saatci, Nathaniel Oberholtzer, Meral Uner, Ozge Akbulut-Caliskan, Metin Cetin, Mertkaya Aras, Kubra Ibis, Burcu Caliskan, Erden Banoglu, Stefan Wiemann, Ayşegül Üner, Sercan Aksoy, Shikhar Mehrotra, Ozgur Sahin
Trastuzumab emtansine (T-DM1) was the first and one of the most successful antibody-drug conjugates (ADCs) approved for treating refractory HER2-positive breast cancer. Despite its initial clinical efficacy, resistance is unfortunately common, necessitating approaches to improve response. Here, we found that in sensitive cells T-DM1 induced spindle assembly checkpoint (SAC)-dependent immunogenic cell death (ICD), an immune-priming form of cell death. The payload of T-DM1 mediated ICD by inducing eIF2α phosphorylation, surface exposure of calreticulin, ATP and HMGB1 release, and secretion of ICD-related cytokines, all of which were lost in resistance...
February 6, 2024: Cancer Research
https://read.qxmd.com/read/38300710/her2-heterogeneity-and-treatment-response-associated-profiles-in-her2-positive-breast-cancer-in-the-nct02326974-clinical-trial
#17
JOURNAL ARTICLE
Zheqi Li, Otto Metzger Filho, Giuseppe Viale, Patrizia dell'Orto, Leila Russo, Marie-Anne Goyette, Avni Kamat, Denise A Yardley, Vandana Gupta Abramson, Carlos L Arteaga, Laura M Spring, Kami Chiotti, Carol Halsey, Adrienne G Waks, Tari A King, Susan C Lester, Jennifer R Bellon, Eric P Winer, Paul T Spellman, Ian E Krop, Kornelia Polyak
BACKGROUND: HER2-targeting therapies have great efficacy in HER2-positive breast cancer, but resistance in part due to HER2 heterogeneity (HET) is a significant clinical challenge. We previously described that in a phase II neoadjuvant trastuzumab emtansine (T-DM1) and pertuzumab (T-DM1+P) clinical trial in early-stage HER2-positive breast cancer, none of the patients with HER2-HET tumors had pathologic complete response (pCR). METHODS: To investigate cellular and molecular differences among tumors according to HER2 heterogeneity and pCR, we performed RNA sequencing (RNA-seq) and ERBB2 FISH of 285 pre/post-treatment tumors from 129 patients in this T-DM1+P neoadjuvant trial...
February 1, 2024: Journal of Clinical Investigation
https://read.qxmd.com/read/38295890/lung-toxicity-induced-by-anti-her2-antibody-drug-conjugates-for-breast-cancer
#18
REVIEW
Mengting Chai, Li Li, Huachao Wu, Yue Liu, Zongbi Yi, Haijun Yu
Human epidermal growth factor receptor 2 (HER2) serves as both a prognostic indicator and a therapeutic target for breast cancer. Therefore, anti-HER2 therapy plays a crucial role in the treatment of HER2 positive cancer. Antibody-drug conjugates (ADCs) are composed of a monoclonal antibody, a chemical linker and a payload, wherein their aim is to reduce the toxicity associated with chemotherapy drugs by utilizing specific antibodies. Among the anti-HER2 ADCs currently approved for clinical use, trastuzumab emtansine(T-DM1) and trastuzumab deruxtecan (T-Dxd) have demonstrated remarkable efficacy in treating HER2 positive breast cancer...
January 29, 2024: Critical Reviews in Oncology/hematology
https://read.qxmd.com/read/38272150/radiation-therapy-tissue-radiosensitization-and-potential-synergism-in-the-era-of-novel-antibody-drug-conjugates
#19
REVIEW
Stefano Natangelo, Dario Trapani, Chrysanthi Koukoutzeli, Luca Boscolo Bielo, Giulia Marvaso, Barbara Alicja Jereczek-Fossa, Giuseppe Curigliano
Antibody-drug conjugates (ADCs) represent a therapeutic class of agents designed to selectively deliver cytotoxic payloads to cancer cells. With the increasingly positioning of ADCs in the clinical practice, combinations with other treatment modalities, including radiation therapy (RT), will open new opportunities but also challenges. This review evaluates ADC-RT interactions, examining therapeutic synergies and potential caveats. ADC payloads can be radiosensitizing, enhancing cytotoxicity when used in combination with RT...
January 24, 2024: Critical Reviews in Oncology/hematology
https://read.qxmd.com/read/38215985/branched-pegylated-linker-auristatin-to-control-hydrophobicity-for-the-production-of-homogeneous-minibody-drug-conjugate-against-her2-positive-breast-cancer
#20
JOURNAL ARTICLE
Emmanuel Douez, Emilie Allard-Vannier, Imène Ait Mohamed Amar, Louis Jolivet, Fanny Boursin, Aurélie Maisonial-Besset, Tiffany Witkowski, Jean-Michel Chezal, Cyril Colas, Stéphanie Letast, Etienne Auvert, Caroline Denevault-Sabourin, Nicolas Aubrey, Nicolas Joubert
Trastuzumab emtansine (Kadcyla®) was the first antibody-drug conjugate (ADC) approved by the Food and Drug Administration in 2013 against a solid tumor, and the first ADC to treat human epidermal growth factor receptor 2 positive (HER2+) breast cancer. However, this second generation ADC is burden by several limitations included heterogeneity, limited activity against heterogeneous tumor (regarding antigen expression) and suboptimal tumor penetration. To address this, different development strategies are oriented towards homogeneous conjugation, new drugs, optimized linkers and/or smaller antibody formats...
January 10, 2024: Journal of Controlled Release
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