Abstract 1901
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.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
4925 - Prognostic role of CD73 in metastatic Non Small Cell Lung Cancer according to the presence of driver alterations
Presenter: Giulia Galli
Session: Poster Display session 1
Resources:
Abstract
785 - JAK-STAT inhibitor overcomes interferon γ-reduced, NK cell-mediated cytotoxicity in non-small-cell lung cancer cells
Presenter: Riki Okita
Session: Poster Display session 1
Resources:
Abstract
2326 - Low LATS2 expression is associated with poor prognosis in non small cell lung cancer
Presenter: Si-hyong Jang
Session: Poster Display session 1
Resources:
Abstract
5960 - Application of ESCAT and OncoKB scales in Liquid biopsy (LB) in Advanced NSCLC patients (pts): Is it feasible and reliable?
Presenter: Michael McCusker
Session: Poster Display session 1
Resources:
Abstract
4855 - IDH1R132H mutation induces a less aggressive phenotype of glioma cells and affects the radiosensitivity by interacting with Wnt/β-catenin signaling
Presenter: Xuetao Han
Session: Poster Display session 1
Resources:
Abstract
2641 - Impact of Angiopoietin-2 on glioblastoma response to combined chemo-radiotherapy
Presenter: Charly Helaine
Session: Poster Display session 1
Resources:
Abstract
5743 - The Discovery of RNA-aptamers That Selectively Bind and Inhibit Glioblastoma Stem Cells by targeting EphA2
Presenter: Alessandra Affinito
Session: Poster Display session 1
Resources:
Abstract
4160 - Impact of tumor reoxygenation by nanoparticles on Tumor Associated Macrophages (TAMs)
Presenter: Aurélie Ferré
Session: Poster Display session 1
Resources:
Abstract
2474 - Prognostic significance of c-Rel/p50 heterodimer in the tumor microenvironment of uveal melanoma
Presenter: Seema Kashyap
Session: Poster Display session 1
Resources:
Abstract
1769 - Synergistic role of BAP1 and DNA damage response pathway in uveal melanoma and its prognostic significance.
Presenter: JAYANTI JHA
Session: Poster Display session 1
Resources:
Abstract