Safety and tolerability of metastasis-directed radiation therapy in the era of evolving systemic, immune, and targeted therapies Review


Authors: Guimond, E.; Tsai, C. J.; Hosni, A.; O'Kane, G.; Yang, J.; Barry, A.
Review Title: Safety and tolerability of metastasis-directed radiation therapy in the era of evolving systemic, immune, and targeted therapies
Abstract: AbstractPurpose: Systemic, immune, and target therapies are growing in use in the management of metastatic cancers. The aim of this review was to describe up-to-date published data on the safety and tolerability of metastasis-directed hypofractionated radiation therapy (RT) when combined with newer systemic, immune, and targeted therapies and to provide suggested strategies to mitigate potential toxicities in the clinical setting. Methods and Materials: A comprehensive search was performed for the time period between 1946 and August 2021 using predetermined keywords describing the use of noncentral nervous system palliative RT with commonly used targeted systemic therapies on PubMed and Medline databases. A total of 1022 articles were screened, and 130 met prespecified criteria to be included in this review. Results: BRAF and MEK inhibitors are reported to be toxic when given concurrently with RT; suspension 3 days and 1 to 2 days, respectively, prior and post-RT is suggested. Cetuximab, erlotinib/gefitinib, and osimertinib were generally safe to use concomitantly with conventional radiation. But in a palliative/hypofractionated RT setting, suspending cetuximab during radiation week, erlotinib/gefitinib 1 to 2 days, and osimertinib ≥2 days pre- and post-RT is suggested. Vascular endothelial growth factor inhibitors such as bevacizumab reported substantial toxicities, and the suggestion is to suspend 4 weeks before and after radiation. Less data exist on sorafenib and sunitinib; 5 to 10 days suspension before and after RT should be considered. As a precaution, until further data are available, for cyclin-dependent kinase 4-6 inhibitors, consideration of suspending treatment 1 to 2 days before and after RT should be given. Ipilimumab should be suspended 2 days before and after RT, and insufficient data exist for other immunotherapy agents. Trastuzumab and pertuzumab are generally safe to use in combination with RT, but insufficient data exist for other HER2 target therapy. Conclusions: Suggested approaches are described, using up-to-date literature, to aid clinicians in navigating the integration of newer targeted agents with hypofractionated palliative and/or ablative metastatic RT. Further prospective studies are required. © 2022
Keywords: drug tolerability; review; sorafenib; bevacizumab; erlotinib; sunitinib; drug safety; systemic therapy; unspecified side effect; cancer radiotherapy; antineoplastic agent; cancer palliative therapy; ipilimumab; cancer immunotherapy; metastasis; vasculotropin inhibitor; cetuximab; gefitinib; medline; trastuzumab; cytotoxic t lymphocyte antigen 4; cyclin dependent kinase inhibitor; chemoradiotherapy; epidermal growth factor receptor kinase inhibitor; pertuzumab; b raf kinase inhibitor; molecularly targeted therapy; trastuzumab emtansine; mitogen activated protein kinase kinase inhibitor; immune checkpoint inhibitor; combination drug therapy; hypofractionated radiotherapy; human; anaplastic lymphoma kinase inhibitor; osimertinib
Journal Title: Advances in Radiation Oncology
Volume: 7
Issue: 6
ISSN: 2452-1094
Publisher: Elsevier Inc.  
Date Published: 2022-11-01
Start Page: 101022
Language: English
DOI: 10.1016/j.adro.2022.101022
PROVIDER: scopus
PMCID: PMC9513086
PUBMED: 36177487
DOI/URL:
Notes: Review -- Export Date: 1 November 2022 -- Source: Scopus
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  1. Jonathan T Yang
    166 Yang
  2. Chiaojung Jillian   Tsai
    239 Tsai