ESMO-ESTRO consensus statements on the safety of combining radiotherapy with EGFR, ALK, or BRAF/MEK inhibitors
ESMO/ESTRO · 2026 · Europe
Source and licence
- Authors
- ESM van Aken, SM O’Cathail, AK Gandhi et al.
- Title
- ESMO-ESTRO consensus statements on the safety of combining radiotherapy with EGFR, ALK, or BRAF/MEK inhibitors
- Journal
- ESMO Open, 2026
- Licence
- CC BY 4.0
- Changes
- Verbatim excerpts; formatting adapted
Full text retrieved 2026-10-27 from Europe PMC · PMC12955645
Licence statement of the original publication
This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
This page reproduces excerpts of the original publication; the original is authoritative. It has not been reviewed by a physician, does not state a recommendation of Medelix and does not replace medical advice. The guideline may have been updated since.
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Recommendations
Verbatim, with grade of recommendation or strength of consensus where given.
Drug class and systematic literature review summary
- Information on the combination of ALK inhibitors and RT is scarce and consists of case reports and small retrospective series. Most data available are about RT to the central nervous system (CNS). Based on available biological/pharmacological data, it can be hypothesized that survival and repopulation of (particularly fast dividing) normal tissues could be reduced by ALK inhibitors after RT, thus increasing the toxicity of RT. Most interactions could be expected in days-to-weeks after RT (acute phase). However, evidence is scarce and what is available, primarily applies to crizotinib. A case of severe (grade 4) esophagitis has been reported with crizotinib and 10 × 3 Gy on the cervical spine. Gamma Knife RT for brain metastases seemed safe during crizotinib therapy. However, it should be noted that crizotinib is the only ALK inhibitor reported to not cross the blood–brain barrier, whereas CNS-penetrant ALK inhibitors may have a greater potential for side effects when combined with CNS-directed RT.
Abstract
Background: Combining radiotherapy (RT) with targeted agents may lead to improved treatment outcomes across various tumor types. However, there is a risk of increased toxicity. Unfortunately, high-quality toxicity data are scarce, contributing to a lack of evidence-based guidelines.
Design: ESMO and ESTRO launched a series of systematic literature reviews and evidence-based, multidisciplinary Delphi consensus recommendations on the safety of combining RT with targeted agents. The current paper addresses the safety of combining EGFR, ALK, and BRAF/MEK inhibitors with RT, regardless of (solid) tumor histology. During the two Delphi consensus rounds with 19 international experts, 57 clinical scenarios were evaluated by systematically covering different drug classes and irradiated areas. Based on the systematic literature reviews, safety statements were developed for all scenarios.
Results: During the systematic literature review process for EGFR, ALK, and BRAF/MEK inhibitors, 2745 records were screened, and 110 reports were included in the final literature reviews and the database. Over the course of the subsequent Delphi consensus rounds, agreement was reached on all 57 scenario-specific safety statements.
Conclusions: For most scenarios, concurrently combining RT with targeted agents may lead to increased toxicity. Therefore, we recommend a drug interruption, a drug dosage reduction, or a major RT adaptation in various scenarios.
Contents of the original publication
The section headings of the original.
- Introduction
- Methods
- Project governance
- Systematic literature reviews
- Literature database
- Safety recommendations
- Modified Delphi process
- Results
- EGFR inhibitors
- Delphi consensus recommendations
- ALK inhibitors
- BRAF/MEK inhibitors
- Discussion
- Supplementary data
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