Safety profile of trastuzumab-emtansine (T-DM1) with concurrent radiation therapy: A systematic review and meta-analysis.


Journal

Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology
ISSN: 1879-0887
Titre abrégé: Radiother Oncol
Pays: Ireland
ID NLM: 8407192

Informations de publication

Date de publication:
09 2023
Historique:
received: 07 03 2023
revised: 02 07 2023
accepted: 04 07 2023
medline: 21 8 2023
pubmed: 13 7 2023
entrez: 12 7 2023
Statut: ppublish

Résumé

In recent years, the treatment landscape for breast cancer has undergone significant advancements, with the introduction of several new anticancer agents. One such agent is trastuzumab emtansine (T-DM1), an antibody drug conjugate that has shown improved outcomes in both early and advanced breast cancer. However, there is currently a lack of comprehensive evidence regarding the safety profile of combining T-DM1 with radiation therapy (RT). In this study, we aim to provide a summary of the available data on the safety of combining RT with T-DM1 in both early and metastatic breast cancer settings. This systematic review and meta-analysis project is part of the consensus recommendations by the European Society for Radiotherapy and Oncology (ESTRO) Guidelines Committee on integrating RT with targeted treatments for breast cancer. A thorough literature search was conducted using the PUBMED/MedLine, Embase, and Cochrane databases to identify original studies focusing on the safety profile of combining T-DM1 with RT. After applying eligibility criteria, nine articles were included in the meta-analysis. Pooled data from these studies revealed a high incidence of grade 3 + radionecrosis (17%), while the rates of grade 3 + radiation-related pneumonitis (<1%) and skin toxicity (1%) were found to be very low. Although there is some concern regarding a slight increase in pneumonitis when combining T-DM1 with postoperative RT, the safety profile of this combination was deemed acceptable for locoregional treatment in non-metastatic breast cancer. However, caution is advised when irradiating intracranial sites concurrently with T-DM1. There is a pressing need for international consensus guidelines regarding the safety considerations of combining T-DM1 and RT for breast cancer.

Sections du résumé

BACKGROUND AND PURPOSE
In recent years, the treatment landscape for breast cancer has undergone significant advancements, with the introduction of several new anticancer agents. One such agent is trastuzumab emtansine (T-DM1), an antibody drug conjugate that has shown improved outcomes in both early and advanced breast cancer. However, there is currently a lack of comprehensive evidence regarding the safety profile of combining T-DM1 with radiation therapy (RT). In this study, we aim to provide a summary of the available data on the safety of combining RT with T-DM1 in both early and metastatic breast cancer settings.
MATERIALS AND METHODS
This systematic review and meta-analysis project is part of the consensus recommendations by the European Society for Radiotherapy and Oncology (ESTRO) Guidelines Committee on integrating RT with targeted treatments for breast cancer. A thorough literature search was conducted using the PUBMED/MedLine, Embase, and Cochrane databases to identify original studies focusing on the safety profile of combining T-DM1 with RT.
RESULTS
After applying eligibility criteria, nine articles were included in the meta-analysis. Pooled data from these studies revealed a high incidence of grade 3 + radionecrosis (17%), while the rates of grade 3 + radiation-related pneumonitis (<1%) and skin toxicity (1%) were found to be very low.
CONCLUSION
Although there is some concern regarding a slight increase in pneumonitis when combining T-DM1 with postoperative RT, the safety profile of this combination was deemed acceptable for locoregional treatment in non-metastatic breast cancer. However, caution is advised when irradiating intracranial sites concurrently with T-DM1. There is a pressing need for international consensus guidelines regarding the safety considerations of combining T-DM1 and RT for breast cancer.

Identifiants

pubmed: 37437610
pii: S0167-8140(23)00343-2
doi: 10.1016/j.radonc.2023.109805
pii:
doi:

Substances chimiques

Ado-Trastuzumab Emtansine SE2KH7T06F
Trastuzumab P188ANX8CK
Receptor, ErbB-2 EC 2.7.10.1
Antibodies, Monoclonal, Humanized 0
Maytansine 14083FR882

Types de publication

Meta-Analysis Systematic Review Journal Article Review Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

109805

Informations de copyright

Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Auteurs

Viola Salvestrini (V)

Department of Experimental and Clinical Biomedical Sciences "M. Serio", University of Florence, Florence, Italy; Radiation Oncology Unit, Oncology Department, Azienda Ospedaliero Universitaria Careggi, Florence, Italy.

Kyubo Kim (K)

Department of Experimental and Clinical Biomedical Sciences "M. Serio", University of Florence, Florence, Italy; Department of Radiation Oncology, Ewha Womans University College of Medicine, Seoul, Republic of Korea.

Saverio Caini (S)

Cancer Risk Factors and Lifestyle Epidemiology Unit, Institute for Cancer Research, Prevention and Clinical Network (ISPRO), Florence, Italy.

Sara Alkner (S)

Department of Hematology, Oncology, and Radiation Physics, Skåne University Hospital, Lund, Sweden; Lund University Cancer Centre, Department of Clinical Sciences, Lund University, Lund, Sweden.

Maria Ekholm (M)

Department of Oncology, Region Jönköping County, Sweden; Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden.

Tanja Skyttä (T)

Tampere University Hospital, Tampere, Finland.

Carlotta Becherini (C)

Department of Experimental and Clinical Biomedical Sciences "M. Serio", University of Florence, Florence, Italy; Radiation Oncology Unit, Oncology Department, Azienda Ospedaliero Universitaria Careggi, Florence, Italy.

Charlotte E Coles (CE)

Department of Oncology, University of Cambridge, Cambridge, UK.

Orit Kaidar-Person (O)

Breast Cancer Radiation Therapy Unit, Sheba Medical Center, Ramat Gan, Israel; The Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel; GROW-School for Oncology and Reproductive (Maastro), Maastricht University, Maastricht, the Netherlands.

Birgitte Offersen (B)

Department of Experimental Clinical Oncology, Danish Centre for Particle Therapy, Department of Oncology, Aarhus University Hospital, Aarhus, Denmark.

Evandro de Azambuja (E)

Institut Jules Bordet and l'Université Libre de Bruxelles (U.L.B), Brussels, Belgium.

Luca Visani (L)

Department of Experimental and Clinical Biomedical Sciences "M. Serio", University of Florence, Florence, Italy; Radiation Oncology Unit, Oncology Department, Azienda Ospedaliero Universitaria Careggi, Florence, Italy.

Javier Cortes (J)

International Breast Cancer Center (IBCC), Pangaea Oncology, Quironsalud Group & Medical Scientia Innovation Research (MedSIR), Barcelona, Spain; Faculty of Biomedical and Health Sciences, Department of Medicine, Universidad Europea de Madrid, Madrid, Spain.

Nadia Harbeck (N)

Department of Gynecology and Obstetrics and CCCMunich, Breast Center, LMU University Hospital, Munich, Germany.

Hope S Rugo (HS)

UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, CA, USA.

Clare M Isacke (CM)

Breast Cancer Now Research Centre, The Institute of Cancer Research, London, UK.

Elisabetta Marangoni (E)

Laboratory of Preclinical Investigation, Translational Research Department, Institut Curie, Paris, France.

Andrea Morandi (A)

Department of Experimental and Clinical Biomedical Sciences "M. Serio", University of Florence, Florence, Italy.

Matteo Lambertini (M)

Department of Internal Medicine and Medical Specialties (DiMI), School of Medicine, University of Genova, Genova, Italy; Department of Medical Oncology, UOC Clinica di Oncologia Medica, IRCCS Ospedale Policlinico San Martino, Genova, Italy.

Philip Poortmans (P)

Department of Radiation Oncology, Iridium Netwerk, Wilrijk, Antwerp, Belgium; Faculty of Medicine and Health Sciences, University of Antwerp, Wilrijk, Antwerp, Belgium.

Lorenzo Livi (L)

Department of Experimental and Clinical Biomedical Sciences "M. Serio", University of Florence, Florence, Italy; Radiation Oncology Unit, Oncology Department, Azienda Ospedaliero Universitaria Careggi, Florence, Italy.

Icro Meattini (I)

Department of Experimental and Clinical Biomedical Sciences "M. Serio", University of Florence, Florence, Italy; Radiation Oncology Unit, Oncology Department, Azienda Ospedaliero Universitaria Careggi, Florence, Italy. Electronic address: icro.meattini@unifi.it.

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Classifications MeSH