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
3620 - Safety, efficacy, PK and PD biomarker results of the first-in-human study of mutant isocitrate dehydrogenase 1 (mIDH1) inhibitor BAY 1436032 in patients (pts) with mIDH1 advanced solid tumours
Presenter: Wolfgang Wick
Session: Poster Display session 1
Resources:
Abstract
5465 - Proof of concept clinical study by US-guided intratumor injection of VCN-01, an oncolytic adenovirus expressing hyaluronidase in patients with pancreatic cancer
Presenter: Manuel Hidalgo
Session: Poster Display session 1
Resources:
Abstract
2555 - A Phase 1a/b first-in-human, open-label, dose-escalation, safety, PK and PD study of TP-0903 in solid tumors
Presenter: John Sarantopoulos
Session: Poster Display session 1
Resources:
Abstract
3533 - First in human phase 1/2a study of PEN-866, a Heat Shock Protein 90 (HSP90) ligand – SN38 conjugate for patients with advanced solid tumors: Phase 1 results
Presenter: Johanna Bendell
Session: Poster Display session 1
Resources:
Abstract
4114 - A Phase I Open-Label, Non-Randomized Study of Recombinant Super-Compound Interferon (rSIFN-co) In Patients with Advanced Solid Tumors
Presenter: Amanda Seet
Session: Poster Display session 1
Resources:
Abstract
2537 - Evaluation of Pharmacodynamic (PD) Biomarkers in Advanced Cancer Patients Treated with Oxidative Phosphorylation (OXPHOS) Inhibitor, OPC-317 (OPC)
Presenter: Jie Qing Eu
Session: Poster Display session 1
Resources:
Abstract
5764 - Pharmacokinetic (PK) assessment of BT1718: A phase 1/2a study of BT1718, a first in class Bicycle Toxin Conjugate (BTC), in patients (pts) with advanced solid tumours
Presenter: Natalie Cook
Session: Poster Display session 1
Resources:
Abstract
2683 - A phase I open label dose escalation trial evaluating VT1021 in patients with advanced solid tumors.
Presenter: Wael Harb
Session: Poster Display session 1
Resources:
Abstract
3609 - Interim Results from Trial of SL-801, a Novel XPO-1 Inhibitor, in Patients with Advanced Solid Tumors
Presenter: Judy Wang
Session: Poster Display session 1
Resources:
Abstract
3485 - Phase 1 Trial of Fruquintinib in Patients with Advanced Solid Tumors: Results of the Dose Escalation Phase
Presenter: Andrea Wang-Gillam
Session: Poster Display session 1
Resources:
Abstract