Adverse Events in Placebo Arms of Cancer Trials

Abstract

Background/Aim: Adverse events (AEs) in cancer trials may be caused by the investigational agents or the underlying disease. Determining the causality is challenging, especially in early cancer drug development when a control arm is lacking. Materials and Methods: We carried out a systematic literature review of AE frequencies in placebo arms of randomized trials for malignant solid tumors and hematologic malignancies reported in PubMed from 2016 to January 2022. Results: Among 148 placebo arms, the AEs with the highest reported mean frequencies among all publications were: Fatigue (20.1%), nausea (16.3%), diarrhea (14.3%), abdominal pain (12.4%), and anemia (10.9%); AEs resulting in drug discontinuation were reported in 5.6% of placebo-treated patients and serious AEs in 18.7% of placebo patients. Conclusion: The data presented here may be used as a benchmark to help assess drug causality in early development cancer studies without a control arm.