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
5011 - LCSCAF1 maintains cancer stem-like traits by stabilizing c-Myc protein and promotes metastasis and recurrence in lung cancer
Presenter: Tao Guo
Session: Poster Display session 1
Resources:
Abstract
4955 - XAF1 Enhances Temozolomide Induced Autophagic Cell Death through AMPK signaling pathway
Presenter: Mingoo Lee
Session: Poster Display session 1
Resources:
Abstract
5616 - The effect of cortisol on methylation patterns in breast cancer cell lines
Presenter: Haya Intabli
Session: Poster Display session 1
Resources:
Abstract
4649 - Global and sex-specific epigenome-wide association studies for the identification of the main methylated loci related to smoking in a Mediterranean population
Presenter: Judith Begona Ramirez Sabio
Session: Poster Display session 1
Resources:
Abstract
4984 - Whole transcriptomics analyses of mimicking Circulating Tumor Cells (CTCs) by single-cell RNA sequencing (scRNAseq)
Presenter: Jessica Garcia
Session: Poster Display session 1
Resources:
Abstract
5926 - Comparison of enzymatic- and bisulfite conversion to map the plasma cell-free methylome in cancer
Presenter: Nicole Lambert
Session: Poster Display session 1
Resources:
Abstract
5454 - Detection of low mutations in hepatocellular carcinoma by using circulating tumor DNA
Presenter: Esl Kim
Session: Poster Display session 1
Resources:
Abstract
4428 - Variants in the JAK1 and JAK2 genes in the risk and prognosis of patients with cutaneous melanoma
Presenter: Bruna Carvalho
Session: Poster Display session 1
Resources:
Abstract
4409 - P-Rex1 expression in breast cancer patients.
Presenter: Angela Lara Montero
Session: Poster Display session 1
Resources:
Abstract
4185 - Modulation of Risk of Cutaneous Melanoma Patients by Variants in STAT3 Gene and Functional Analysis
Presenter: Gabriela Gomez
Session: Poster Display session 1
Resources:
Abstract