ESMO-ESTRO consensus statements on the safety of combining radiotherapy with CDK4/6, HER2, PARP, or mTOR inhibitors

Background: While combining radiotherapy (RT) with targeted agents or immunotherapy may improve outcomes, it may also increase toxicity. High-quality toxicity data and multidisciplinary, evidence-based guidelines on the combination of these treatment modalities are scarce. Design: The European Society for Medical Oncology (ESMO) and the European SocieTy for Radiotherapy and Oncology (ESTRO) developed a series of systematic reviews with multidisciplinary, tumor-agnostic, evidence-based Delphi consensus statements regarding the safety of combining RT with targeted agents or immunotherapy. The current study addresses the safety of combining RT with CDK4/6 inhibitors, anti-HER2 monoclonal antibodies, PARP inhibitors, or mTOR-inhibitors. During the modified Delphi process, two digital voting rounds were organized with 18 international experts. By systematically evaluating the different drug classes and irradiated areas, 74 clinical scenarios were assessed. Safety statements were formulated for all scenarios, based on the evidence from the systematic literature reviews. Results: A total of 1,341 records were screened during the systematic literature reviews, of which 107 studies were ultimately included in the final reviews and the literature database. After two Delphi voting rounds, agreement was reached on all 74 scenario-specific safety statements. Conclusions: The expected combined toxicity is often low for anti-HER2 monoclonal antibodies. For most scenarios with CDK4/6, PARP, or mTOR inhibitors, exercising caution is recommended.