1839PPlacebo adverse events (AEs) in targeted and immune cancer therapy in the adjuvant and advanced setting: A systematic review and meta-analysis

Abstract Background AEs resulting from placebo administration have not been well studied in oncology. The aim of this study was to describe the incidence of AEs in the placebo arms of target and immunotherapy cancer drugs in all treatment settings, and to analyze their relation with AEs reported in the active arms of included trials. Methods Based on PRISMA guidelines, a systematic literature search was performed including phase 3, randomized, double-blind, placebo-controlled trials from 1/1/2000 to 1/5/19. Adjuvant and advanced-stage studies using targeted and immunotherapy were included. Trials involving active anticancer treatment in addition to placebo in the control group were excluded. Random-effects meta-analysis was performed to estimate the incidence of grade 3-4 placebo AEs. Results Of 4396 studies screened, 40 trials were eligible (adjuvant n = 14; advanced n = 26) including 10 cancer types and 28,520. Median incidence of any-grade placebo AEs was 90% (IQR 89-91%) in the adjuvant and 89.5% (IQR 72-96%) in the advanced trials. Grade 5 drug-related AEs were reported in 19 pts receiving placebo. 4 trials reported a higher frequency of grade 3-4 AEs in the placebo arm than in the active treatment arm. The overall, random-effects pooled incidence of grade 3-4 placebo AEs was 22% (95% CI, 17-27%; [I2= 95%]) for the adjuvant and 27% (95% CI, 20-35%; [I2= 97%]) for the advanced trials. No statistical differences were observed comparing both settings (Wilcoxon rank-sum test, P = 0.2). Frequency of grade 3-4 placebo AEs was found to be correlated between the treatment and placebo arms in both adjuvant (ρ = 0.5; P = .042) and advanced studies (ρ = 0.6; P = .003). Conclusions Placebo administration was associated with a substantial incidence of grade 3-4 placebo AEs in adjuvant and advanced settings. An association between the active treatment and placebo arms was observed in both scenarios. These findings should be taken into consideration by the medical community in the toxicity evaluation criteria of a placebo-controlled clinical trial. Legal entity responsible for the study The authors. Funding Has not received any funding. Disclosure All authors have declared no conflicts of interest.