Expert recommendations on treatment sequencing and challenging clinical scenarios in human epidermal growth factor receptor 2-positive (HER2-positive) metastatic breast cancer
- PMID: 39580869
- DOI: 10.1016/j.ctrv.2024.102853
Expert recommendations on treatment sequencing and challenging clinical scenarios in human epidermal growth factor receptor 2-positive (HER2-positive) metastatic breast cancer
Abstract
Human epidermal growth factor receptor 2 (HER2) overexpression and/or ERBB2 gene amplification occurs in approximately 15-20% of breast cancers and is associated with poor prognosis. While the introduction of HER2-targeted therapies has significantly improved survival in patients with HER2-positive metastatic breast cancer, the incidence of brain metastases has increased due to patients living longer. Current recommendations sequence treatments by line of therapy, as well as by the status of brain metastases in patients with HER2-positive breast cancer. However, in the third-line treatment setting and beyond, there is a lack of clarity of the preferred choice of therapy. In clinical practice, clinicians may also encounter challenging scenarios where the optimal therapeutic approach has not been defined by clinical studies, so there is a need for clarity in such situations. Two consensus meetings of expert oncologists (12 from Europe and one from Canada) were convened to discuss these scenarios. We subsequently developed this article to present an overview of current treatment recommendations for HER2-positive metastatic breast cancer and give practical guidance on addressing challenging scenarios in a real-world setting. Based on our clinical experience, we provide a unanimous consensus concerning the treatment of elderly patients as well as those with brain-only metastases, leptomeningeal disease, oligometastatic disease, central nervous system oligo-progressive disease or ERBB2-mutant disease. We also discuss how to combine HER2-targeted therapy with endocrine therapy in patients with HER2-positive/hormone-receptor-positive disease, considerations for potential discontinuation of HER2-targeted therapy in patients with long-term remission and how to treat patients whose metastatic biopsy no longer confirms their HER2-positive status.
Keywords: Brain metastases; Challenging clinical scenario; Expert consensus; HER2-positive; Metastatic breast cancer; Real-world; Treatment sequencing.
Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.
Conflict of interest statement
Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Rupert Bartsch reports advisory roles at AstraZeneca, Daiichi Sankyo, Eisai, Eli Lilly, Grünenthal, MSD, Novartis, Pfizer, Pierre Fabre, Roche and Seagen; lecture honoraria from AstraZeneca, Daiichi Sankyo, Eisai, Eli Lilly, Grünenthal, MSD, Novartis, Pfizer, Pierre Fabre, Roche, and Seagen; and research support from Daiichi Sankyo; David Cameron reports fees paid to the institute for advisory roles or talks from AstraZeneca, Daiichi Sankyo, Eli Lilly, Exact Sciences, Gilead Sciences, GSK, Novartis, Pfizer, Pierre Fabre, Roche, Seagen, Synthon, and Zymeworks; Eva Ciruelos reports consulting fees from AstraZeneca, Daiichi Sankyo, Eli Lilly, MSD, Novartis, Pfizer, and Roche; honoraria for speakers’ bureaus from Eli Lilly and Roche; and support for attending meetings from Pfizer and Roche; Carmen Criscitiello reports personal fees for consulting, advisory roles, and speakers’ bureaus from AstraZeneca, Daiichi Sankyo, Eli Lilly, Gilead Sciences, MSD, Novartis, Pfizer, Roche, and Seagen; Giuseppe Curigliano reports honoraria for speaker’s engagement from Bristol Myers-Squibb, Celltrion, Eli Lilly, Foundation Medicine, MSD, NanoString, Novartis, Pfizer, Roche, Samsung, and Seagen; honoraria for providing consultancy from NanoString, Roche, and Seagen; honoraria for participating on the advisory boards of Celltrion, Eli Lilly, Foundation Medicine, Mylan, Pfizer, Roche, and Samsung; honoraria for writing engagement from Bristol Myers-Squibb and Novartis; honoraria for participation in the Ellipsis Scientific Affairs Group; institutional research funding for conducting phase 1 and 2 clinical trials from AbbVie, AstraZeneca, Bayer, Bristol Myers-Squibb, Celgene, Janssen-Cilag, Medimmune, Medivation, Merck Serono, MSD, Novartis, Orion, Pfizer, Philogen, Roche, Sanofi, Seagen, Servier, and Tesaro; Francois P Duhoux reports a postdoctoral research grant from Fondation Belge contre le Cancer; consulting fees from Amgen, AstraZeneca, Daiichi Sankyo, Eli Lilly, Gilead Sciences, MSD, Novartis, Pfizer, Pierre Fabre, Roche, and Seagen; and travel support from Amgen, AstraZeneca, Daiichi Sankyo, Gilead Sciences, Pfizer, Roche, and Teva; Theodoros Foukakis reports advisory roles with Affibody, Exact Sciences, Novartis, and Veracyte; speaker roles with Pfizer; royalties for authorship of two chapters in UpToDate: Wolters Kluwer; serving as a coordinating principal investigator for trials with AstraZeneca, Novartis, Pfizer, and Veracyte; clinical trial support paid to the institution from AstraZeneca, Novartis, Pfizer, and Veracyte; and fees paid to the institute for speaker roles with AstraZeneca, Gilead Sciences, and Roche; Joseph Gligorov reports speakers’ bureau honoraria from Roche-Genentech, Novartis, Eisai, Genomic Health, Ipsen, Pfizer, Mylan, Eli Lilly, Sandoz, and Pierre-Fabre; consultant/advisory board member for Roche-Genentech, Novartis, Onxeo, Daiichi Sankyo, MSD, Eisai, Genomic Health, Ipsen, Macrogenics, Pfizer, Mylan, Eli Lilly, Immunomedics, and Pierre-Fabre; grant support from Roche-Genentech, Eisai, Genomic Health, Pfizer, and Mylan; travel and accommodation paid by Roche-Genentech, Novartis, Eisai, Genomic Health, Pfizer, Eli Lilly, and Pierre-Fabre; personal fees and non-financial support from Daiichi Sankyo and MSD; Nadia Harbeck reports personal fees for lectures and/or consulting from AstraZeneca, Daiichi Sankyo, Eli Lilly, Gilead Sciences, MSD, Novartis, Pierre-Fabre, Pfizer, Roche, Seagen, Viatris, and Zuellig Pharma; Nathalie LeVasseur reports participating in advisory boards for AstraZeneca, Eli Lilly, Gilead Sciences, Merck, Novartis, Pfizer, Roche, Seagen, and TerSera; and research funding paid to their institution from AbbVie, Eli Lilly, Exact Sciences, Gilead Sciences, Novartis, and Pfizer; Alicia Okines has received research funding from Pfizer and Roche; participated in advisory boards for AstraZeneca, Pfizer, Roche, and Seagen; received speakers’ fees from AstraZeneca, Eli Lilly, Eisai, Gilead Sciences, Pfizer, Roche, and Seagen; and received conference support from AstraZeneca, Eli Lily, Novartis, and Roche; Frederique Penault-Llorca has provided consultancy for AbbVie, Amgen, AstraZeneca, Bayer, Bristol Myers-Squibb, Clovis, Daiichi Sankyo, Diaceutics, Eli Lilly, Illumina, Invitae, MSD, Novartis, Pfizer, Seagen, Roche, and Ventana; has received research grants from AbbVie, AstraZeneca, Bayer, Bristol Myers-Squibb, Illumina, MSD, and Roche; and travel and accommodation paid by AbbVie, AstraZeneca, Bayer, BMS, Gilead, MSD, Novartis, Pfizer, and Roche; Volkmar Müller reports speaker honoraria from AstraZeneca, Daiichi Sankyo, Eisai, Eli Lilly, Gilead Sciences, high5 Oncology, iMED Institut, Medac, Medscape, MSD, Novartis, Onkowissen, Pfizer, Pierre Fabre, Roche, and Seagen; consultancy honoraria from Clinsol, Daiichi Sankyo, Eisai, Gilead Sciences, MSD, Novartis, Pierre Fabre, PINK, Roche, Seagen, and Stemline; institutional research support from AstraZeneca, Genentech, Novartis, Roche, and Seagen; and travel grants from AstraZeneca, Daiichi Sankyo, Gilead Sciences, Roche, and Pfizer.
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