Adverse Events in Placebo Arms of Cancer Trials

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.

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.

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.

The data presented here may be used as a benchmark to help assess drug causality in early development cancer studies without a control arm.