Combining radiotherapy and immune checkpoint inhibitors in metastatic cancers: a 25-year review of safety outcomes by the ENRSO Group

This scoping review evaluates the safety and feasibility of combining immune checkpoint inhibitors (ICIs) with radiotherapy (RT) in metastatic cancers. The analysis focuses on key variables that may influence toxicity, including the site of irradiation, the radiation dose, and treatment timing. The primary endpoint was the incidence of grade ≥ 3 adverse events. Following PRISMA guidelines, we conducted a systematic review of 59 studies published between January 2000 and January 2025, selected through a three-step screening process. The dataset included 37 prospective and 22 retrospective studies, encompassing 2 phase III trials and a total of 3593 patients. The median incidence of grade ≥ 3 adverse events ranged from 9.7% to 11% for anti-PD1 agents, 10.5% to 19% for anti-PD-L1 agents, and 20% to 25% for anti-CTLA-4 agents. No clinically significant increase in toxicity was observed when RT was combined with ICI, compared to ICI alone. Available evidence suggests that concurrent ICI and RT is a safe strategy in metastatic cancer, without requiring immunotherapy discontinuation or treatment modification during irradiation.