Systematic review and meta-analysis of TRAEs in patients receiving ICIs for solid tumors in randomized controlled trials

Incorporation of immune checkpoint inhibitors (ICIs) into perioperative cancer therapy has improved clinical outcomes, but also is associated with risk of treatment-related adverse events (TRAEs). Systematic review and meta-analysis of randomized controlled trials investigated TRAEs of addition of ICIs to perioperative therapy for solid tumors. The analysis included 28 trials with 16,796 patients. Addition of ICIs was not significantly associated with grade 5 TRAEs (OR 1.76; p=0.073), but did increase the incidence of grade 3 or 4 TRAEs (2.73; p<0.0001), TRAEs leading to treatment discontinuation (3.67; p<0.0001), and TRAEs of any grade (2.60; p<0.0001). ICI versus placebo as adjuvant therapy was associated with increased incidence of grade 5 TRAEs (OR 4.02; p=0.044) and grade 3-4 TRAEs (5.31; p<0.001) while ICI versus placebo in the neoadjuvant setting was not associated with increased incidence of grade 5 TRAEs (1.11; p=0.84) or grade 3-4 TRAEs (1.17; p=0.23). The authors conclude that addition of ICIs to perioperative therapy for solid tumors was associated with increase in grade 3-4 TRAEs and TRAEs leading to treatment discontinuation.