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Epitranscriptomics & Cancer Adaptation : A.David

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Our research work focuses on the contribution of post-transcriptional mechanisms on cancer cell adaptation, in particular RNA epigenetic & translational control.

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Group name EquipeCTCS
Item Type Journal Article
Title Trastuzumab Deruxtecan in Previously Treated HER2-Low Advanced Breast Cancer
Creator Modi et al.
Author Shanu Modi
Author William Jacot
Author Toshinari Yamashita
Author Joohyuk Sohn
Author Maria Vidal
Author Eriko Tokunaga
Author Junji Tsurutani
Author Naoto T. Ueno
Author Aleix Prat
Author Yee Soo Chae
Author Keun Seok Lee
Author Naoki Niikura
Author Yeon Hee Park
Author Binghe Xu
Author Xiaojia Wang
Author Miguel Gil-Gil
Author Wei Li
Author Jean-Yves Pierga
Author Seock-Ah Im
Author Halle C. F. Moore
Author Hope S. Rugo
Author Rinat Yerushalmi
Author Flora Zagouri
Author Andrea Gombos
Author Sung-Bae Kim
Author Qiang Liu
Author Ting Luo
Author Cristina Saura
Author Peter Schmid
Author Tao Sun
Author Dhiraj Gambhire
Author Lotus Yung
Author Yibin Wang
Author Jasmeet Singh
Author Patrik Vitazka
Author Gerold Meinhardt
Author Nadia Harbeck
Author David A. Cameron
Abstract BACKGROUND: Among breast cancers without human epidermal growth factor receptor 2 (HER2) amplification, overexpression, or both, a large proportion express low levels of HER2 that may be targetable. Currently available HER2-directed therapies have been ineffective in patients with these "HER2-low" cancers. METHODS: We conducted a phase 3 trial involving patients with HER2-low metastatic breast cancer who had received one or two previous lines of chemotherapy. (Low expression of HER2 was defined as a score of 1+ on immunohistochemical [IHC] analysis or as an IHC score of 2+ and negative results on in situ hybridization.) Patients were randomly assigned in a 2:1 ratio to receive trastuzumab deruxtecan or the physician's choice of chemotherapy. The primary end point was progression-free survival in the hormone receptor-positive cohort. The key secondary end points were progression-free survival among all patients and overall survival in the hormone receptor-positive cohort and among all patients. RESULTS: Of 557 patients who underwent randomization, 494 (88.7%) had hormone receptor-positive disease and 63 (11.3%) had hormone receptor-negative disease. In the hormone receptor-positive cohort, the median progression-free survival was 10.1 months in the trastuzumab deruxtecan group and 5.4 months in the physician's choice group (hazard ratio for disease progression or death, 0.51; P<0.001), and overall survival was 23.9 months and 17.5 months, respectively (hazard ratio for death, 0.64; P?=?0.003). Among all patients, the median progression-free survival was 9.9 months in the trastuzumab deruxtecan group and 5.1 months in the physician's choice group (hazard ratio for disease progression or death, 0.50; P<0.001), and overall survival was 23.4 months and 16.8 months, respectively (hazard ratio for death, 0.64; P?=?0.001). Adverse events of grade 3 or higher occurred in 52.6% of the patients who received trastuzumab deruxtecan and 67.4% of those who received the physician's choice of chemotherapy. Adjudicated, drug-related interstitial lung disease or pneumonitis occurred in 12.1% of the patients who received trastuzumab deruxtecan; 0.8% had grade 5 events. CONCLUSIONS: In this trial involving patients with HER2-low metastatic breast cancer, trastuzumab deruxtecan resulted in significantly longer progression-free and overall survival than the physician's choice of chemotherapy. (Funded by Daiichi Sankyo and AstraZeneca; DESTINY-Breast04 ClinicalTrials.gov number, NCT03734029.).
Publication The New England Journal of Medicine
Volume 387
Issue 1
Pages 9-20
Date 2022-07-07
Journal Abbr N Engl J Med
Language eng
DOI 10.1056/NEJMoa2203690
ISSN 1533-4406
Library Catalog PubMed
Extra PMID: 35665782
Tags Antibodies, Monoclonal, Humanized, Antineoplastic Agents, Immunological, Antineoplastic Combined Chemotherapy Protocols, Breast Neoplasms, Camptothecin, clinic, Disease Progression, Female, Humans, Immunoconjugates, Immunohistochemistry, marque, Receptor, ErbB-2, top, Trastuzumab
Date Added 2022/07/29 - 11:36:07
Date Modified 2022/08/01 - 14:36:28
Notes and Attachments PubMed entry (Attachment)


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