Possible Radiation Sensitisation by Trastuzumab Leading to Radiation-Induced Myelitis

Law, Alastair; Evans, Tamasin; Hayward, Richard L; Higgins, G.; Murray, Katherine; Summers, David; Kunkler, Ian

doi:10.1159/000193069

Cited by 7 publications

(5 citation statements)

References 10 publications

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“…Two retrospective studies have shown efficacy of brain irradiation and concomitant trastuzumab. However, a case of possible radiation myelitis has been reported in the literature [ 13 ]. Therefore, it is necessary to remain cautious.…”

Section: Resultsmentioning

confidence: 99%

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

Debbi

Grellier

Loganadane

et al. 2023

Cancers

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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.

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Section: Resultsmentioning

confidence: 99%

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

Debbi

Grellier

Loganadane

et al. 2023

Cancers

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“…However there are same clinical evidences in the literature that Trastuzumab radiosensibilizes human healthy tissues and in this way it could increase the toxicity of the treatment. 21 Currently the most important question remains whether the concomitant therapy with Trastuzumab and RT increases cardiotoxicity of the treatment. In the literature, there are limited data about the safety of concomitant therapy with RT and Trastuzumab.…”

Section: Discussionmentioning

confidence: 99%

Spironolactone ameliorates the cardiovascular toxicity induced by concomitant trastuzumab and thoracic radiotherapy

Yavaş

Çelik

Yavaş

et al. 2017

Reports of Practical Oncology & Radiotherapy

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“…There are same clinical evidences in the literature that trastuzumab also radiosensibilizes human healthy tissues, and in this way, it could increase the toxicity of the treatment. 35 Currently, the most important question remains whether the concomitant therapy with trastuzumab and RT increases cardiotoxicity of the treatment. In the literature, there are limited data about the safety of concomitant therapy with RT and trastuzumab.…”

Section: Discussionmentioning

confidence: 99%

Assessment of concomitant versus sequential trastuzumab on radiation-induced cardiovascular toxicity

et al. 2016

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There are limited data regarding effect of trastuzumab on radiation-induced cardiovascular toxicity when used sequentially or concomitantly. This experimental study aims to investigate effect of trastuzumab on radiation-induced cardiovascular toxicity with respect to the treatment sequence. One hundred and eight female Wistar albino rats were divided into six groups (G): G1 was control, G2 was trastuzumab, and G3 was radiotherapy (RT); G4 and G6 were sequential RT and trastuzumab; and G5 was concomitant RT and trastuzumab groups, respectively. Rats were killed at 6th h, 21st and 70th days after RT; thoracic aorta and heart samples were obtained. Transthoracic echocardiography and functional studies evaluating relaxation of thoracic aorta were performed. Subendothelial edema scores of thoracic aorta samples at 21st and 70th days were higher in RT groups (G3, G4, G5, and G6) ( p < 0.001). There was a deterioration of relaxation responses of thoracic aorta samples in RT groups ( p < 0.001). Cardiac fibrosis (CF) scores revealed detrimental effect of RT beginning from 6th h and trastuzumab from 21st day. RT groups showed further deterioration of CF at 70th day. Ejection fraction, left ventricular mass, and fractional shortening were significantly decreased in G4, G5, and G6. Trastuzumab may increase pathological damage in cardiovascular structures when used with RT regardless of timing.

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Possible Radiation Sensitisation by Trastuzumab Leading to Radiation-Induced Myelitis

Cited by 7 publications

References 10 publications

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

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

Spironolactone ameliorates the cardiovascular toxicity induced by concomitant trastuzumab and thoracic radiotherapy

Assessment of concomitant versus sequential trastuzumab on radiation-induced cardiovascular toxicity

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