Interaction between Radiation Therapy and Targeted Therapies in HER2-Positive Breast Cancer: Literature Review, Levels of Evidence for Safety and Recommendations for Optimal Treatment Sequence

by Selleckchem | Jul 31 2023

Purpose: Over the past twenty years, anti-HER2 targeted therapies have proven to be a revolution in the management of human epidermal growth receptor 2 (HER2)-positive breast cancers. Anti-HER2 therapies administered alone or in combination with chemotherapy have been specifically studied. Unfortunately, the safety of anti-HER2 therapies in combination with radiation remains largely unknown. Thus, we propose a literature review of the risks and safety of combining radiotherapy with anti-HER2 therapies. We will focus on the benefit/risk rationale and try to understand the risk of toxicity in early-stage and advanced breast cancer.

Methods: Research was carried out on the following databases: PubMed, EMBASE, ClinicalTrial.gov, Medline, and Web of Science for the terms "radiotherapy", "radiation therapy", "radiosurgery", "local ablative therapy", and "stereotactic", combined with "trastuzumab", "pertuzumab", "trastuzumab emtansine", "TDM-1", "T-Dxd", "trastuzumab deruxtecan", "tucatinib", "lapatinib", "immune checkpoint inhibitors", "atezolizumab", "pembrolizumab", "nivolumab", "E75 vaccine", "interferon", "anti-IL-2", "anti-IL 12", and "ADC".

Results: Association of radiation and monoclonal antibodies such as trastuzumab and pertuzumab (with limited data) seems to be safe, with no excess risk of toxicity. Preliminary data with radiation and of antibody-drug conjugate of trastuzumab combined cytotoxic (trastuzumab emtansine, trastuzumab deruxtecan), given the underlying mechanism of action, suggest that one must be particularly cautious with the association. The safety of the combination of a tyrosine kinase inhibitor (lapatinib, tucatinib) and radiation remains under-studied. The available evidence suggests that checkpoint inhibitors can be safely administrated with radiation.

Conclusions: HER2-targeting monoclonal antibodies and checkpoint inhibitors can be combined with radiation, apparently with no excess toxicities. Caution is required when associating radiation with TKI and antibody drugs, considering the limited evidence.

Comments:

Title: Safety of Combining Radiotherapy with Anti-HER2 Therapies: A Literature Review

Abstract: Anti-HER2 targeted therapies have revolutionized the management of HER2-positive breast cancers over the past two decades. However, the safety of combining these therapies with radiotherapy remains largely unknown. This literature review aims to assess the risks and safety of combining radiotherapy with anti-HER2 therapies in early-stage and advanced breast cancer. A comprehensive search was conducted using multiple databases, including PubMed, EMBASE, ClinicalTrial.gov, Medline, and Web of Science. Various anti-HER2 therapies were included in the search terms. The review findings indicate that the combination of radiation and monoclonal antibodies, such as trastuzumab and pertuzumab, appears to be safe, with no significant increase in toxicity observed. Preliminary data suggest that caution should be exercised when combining radiation with antibody-drug conjugates, such as trastuzumab emtansine and trastuzumab deruxtecan, due to their cytotoxic mechanisms of action. The safety of combining radiation with tyrosine kinase inhibitors (lapatinib, tucatinib) remains understudied. However, the available evidence suggests that checkpoint inhibitors, such as atezolizumab, pembrolizumab, and nivolumab, can be safely administered with radiation. In conclusion, the combination of HER2-targeting monoclonal antibodies and checkpoint inhibitors with radiation appears to have no excessive toxicities. However, caution is advised when combining radiation with tyrosine kinase inhibitors and antibody drugs due to the limited evidence available.

Keywords: HER2-positive breast cancer, anti-HER2 therapies, radiotherapy, safety, toxicity, monoclonal antibodies, tyrosine kinase inhibitors, checkpoint inhibitors.

1. Introduction
- Significance of anti-HER2 targeted therapies in HER2-positive breast cancers.
- Knowledge gap regarding the safety of combining anti-HER2 therapies with radiotherapy.

2. Methods
- Database search strategy and inclusion criteria.
- Identification of relevant studies and data extraction.

3. Anti-HER2 Therapies and Radiation
3.1. Monoclonal Antibodies (Trastuzumab, Pertuzumab)
- Safety profile and potential toxicities when combined with radiation.
- Evaluation of available evidence.

3.2. Antibody-Drug Conjugates (Trastuzumab Emtansine, Trastuzumab Deruxtecan)
- Cautions and considerations due to cytotoxic mechanisms of action.
- Preliminary data and risk assessment.

3.3. Tyrosine Kinase Inhibitors (Lapatinib, Tucatinib)
- Limited evidence and knowledge gaps.
- Potential risks and safety concerns.

3.4. Checkpoint Inhibitors (Atezolizumab, Pembrolizumab, Nivolumab)
- Safety and feasibility of combining with radiation.
- Assessment of available data.

4. Results and Discussion
- Summary of findings for each category of anti-HER2 therapy.
- Risk-benefit analysis and implications for clinical practice.

5. Conclusions
- Overall safety profile of combining anti-HER2 therapies with radiation.
- Recommendations for future research and clinical considerations.

The literature review provides a comprehensive assessment of the risks and safety considerations associated with combining radiotherapy and various anti-HER2 therapies. It highlights the available evidence and knowledge gaps, aiding clinicians in making informed decisions regarding treatment strategies for HER2-positive breast cancer patients.