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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 Intrathecal trastuzumab versus alternate routes of delivery for HER2-targeted therapies in patients with HER2+ breast cancer leptomeningeal metastases
Creator Lazaratos et al.
Author Anna-Maria Lazaratos
Author Sarah M. Maritan
Author Andrea Quaiattini
Author Ivica Ratosa
Author Emanuela Ferraro
Author Gaia Griguolo
Author Valentina Guarneri
Author Alessia Pellerino
Author Silvia Hofer
Author William Jacot
Author Hans-Joachim Stemmler
Author Marcel P. H. van den Broek
Author Nika Dobnikar
Author Francois Panet
Author Zubin Lahijanian
Author Aki Morikawa
Author Andrew D. Seidman
Author Riccardo Soffietti
Author Lawrence Panasci
Author Kevin Petrecca
Author April A. N. Rose
Author Nathaniel Bouganim
Author Matthew Dankner
Abstract BACKGROUND: Patients with HER2+ breast cancer (BC) frequently develop leptomeningeal metastases (LM). While HER2-targeted therapies have demonstrated efficacy in the neoadjuvant, adjuvant, and metastatic settings, including for parenchymal brain metastases, their efficacy for patients with LM has not been studied in a randomized controlled trial. However, several single-armed prospective studies, case series and case reports have studied oral, intravenous, or intrathecally administered HER2-targeted therapy regimens for patients with HER2+ BC LM. METHODS: We conducted a systematic review and meta-analysis of individual patient data to evaluate the efficacy of HER2-targeted therapies in HER2+ BC LM in accordance with PRISMA guidelines. Targeted therapies evaluated were trastuzumab (intrathecal or intravenous), pertuzumab, lapatinib, neratinib, tucatinib, trastuzumab-emtansine and trastuzumab-deruxtecan. The primary endpoint was overall survival (OS), with CNS-specific progression-free survival (PFS) as a secondary endpoint. RESULTS: 7780 abstracts were screened, identifying 45 publications with 208 patients, corresponding to 275 lines of HER2-targeted therapy for BC LM which met inclusion criteria. In univariable and multivariable analyses, we observed no significant difference in OS and CNS-specific PFS between intrathecal trastuzumab compared to oral or intravenous administration of HER2-targeted therapy. Anti-HER2 monoclonal antibody-based regimens did not demonstrate superiority over HER2 tyrosine kinase inhibitors. In a cohort of 15 patients, treatment with trastuzumab-deruxtecan was associated with prolonged OS compared to other HER2-targeted therapies and compared to trastuzumab-emtansine. CONCLUSIONS: The results of this meta-analysis, comprising the limited data available, suggest that intrathecal administration of HER2-targeted therapy for patients with HER2+ BC LM confers no additional benefit over oral and/or IV treatment regimens. Although the number of patients receiving trastuzumab deruxtecan in this cohort is small, this novel agent offers promise for this patient population and requires further investigation in prospective studies.
Publication Breast (Edinburgh, Scotland)
Volume 69
Pages 451-468
Date 2023-06
Journal Abbr Breast
Language eng
DOI 10.1016/j.breast.2023.04.008
ISSN 1532-3080
Library Catalog PubMed
Extra PMID: 37156650 PMCID: PMC10300571
Tags Antineoplastic Combined Chemotherapy Protocols, Breast Neoplasms, Deruxtecan, Female, Humans, Intrathecal, Leptomeningeal, Meningeal Neoplasms, Prospective Studies, Randomized Controlled Trials as Topic, Receptor, ErbB-2, review, Trastuzumab
Date Added 2023/10/16 - 16:51:20
Date Modified 2023/10/16 - 17:28:09
Notes and Attachments PubMed entry (Attachment)
Texte intégral (Attachment)


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