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

Radiother Oncol. 2023 Sep:186:109805. doi: 10.1016/j.radonc.2023.109805. Epub 2023 Jul 10.

Abstract

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.

Keywords: Breast cancer; Meta-analysis; Radiotherapy; Systematic review; T-DM1; Trastuzumab emtansine.

Publication types

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

MeSH terms

  • Ado-Trastuzumab Emtansine / adverse effects
  • Antibodies, Monoclonal, Humanized
  • Breast Neoplasms* / drug therapy
  • Breast Neoplasms* / pathology
  • Female
  • Humans
  • Maytansine* / adverse effects
  • Receptor, ErbB-2 / analysis
  • Receptor, ErbB-2 / therapeutic use
  • Trastuzumab / adverse effects
  • Treatment Outcome

Substances

  • Ado-Trastuzumab Emtansine
  • Trastuzumab
  • Receptor, ErbB-2
  • Antibodies, Monoclonal, Humanized
  • Maytansine