Systematic review and meta-analysis of adverse events in placebo arms of phase 3 lung cancer trials

Adverse events (AEs) are routinely reported in placebo arms of lung cancer trials, yet these data have not often been systematically synthesized. Systematic review and meta-analysis of published studies investigated the incidence of AEs in placebo arms of phase 3 RCTs for non-small cell lung cancer and small cell lung cancer. Twenty-six RCTs comprising 7,641 placebo-treated patients were included. The pooled incidence of any-grade AEs was 84% (95% CI 78-90), with grade 3 or 4 AEs occurring in 25% (19-32). The most frequent AEs were fatigue (20%), dyspnea (20%), and cough (20%); grade 3 or 4 AEs most commonly included fatigue (4%), dyspnea (3%), pneumonia (2%), and hypertension (2%). Treatment interruption or dose reduction due to AEs occurred in 10% (95% CI 6-15) and discontinuation in 5% (4-8). The authors conclude that placebo-treated patients with lung cancer experience substantial AE burden, maybe attributable to the disease itself and its prior treatment. The scarcity of nocebo-related data underscores the urgent need for future studies to investigate its mechanisms and systematically assess negative expectancy in patients.