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

## TL;DR

This paper provides safety guidelines for combining radiotherapy with specific cancer drugs, finding that many combinations may increase toxicity.

## Contribution

The paper presents consensus-based safety statements for combining radiotherapy with EGFR, ALK, or BRAF/MEK inhibitors, based on systematic reviews and expert agreement.

## Key findings

- Combining radiotherapy with EGFR, ALK, or BRAF/MEK inhibitors may increase toxicity in many scenarios.
- Consensus was reached on 57 clinical scenarios involving these drug–RT combinations.
- Recommendations include drug interruption, dosage reduction, or RT adaptation in various cases.

## Abstract

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.

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.

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.

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.

•This ESMO-ESTRO consensus project assesses the safety of combining RT with targeted therapies.•Consensus was reached for all 57 scenarios involving RT combined with EGFR, ALK, or BRAF/MEK inhibitors.•Combining RT with EGFR, ALK, or BRAF/MEK inhibitors may lead to increased toxicity in many scenarios.•Caution is recommended for most of these drug–RT combinations.

This ESMO-ESTRO consensus project assesses the safety of combining RT with targeted therapies.

Consensus was reached for all 57 scenarios involving RT combined with EGFR, ALK, or BRAF/MEK inhibitors.

Combining RT with EGFR, ALK, or BRAF/MEK inhibitors may lead to increased toxicity in many scenarios.

Caution is recommended for most of these drug–RT combinations.