ESMO-ESTRO consensus statements on the safety of combining radiotherapy with EGFR, ALK, or BRAF/MEK inhibitors

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.