Response rates, survival status and adverse events of placebo in randomized control trials for hepatocellular...

In randomized controlled trials (RCTs), the placebo arm has often been ignored as the attention tends to be focused on the treatment arm. We undertook a meta-analysis based on the data from the placebo arm in RCTs of hepatocellular carcinoma (HCC), the response rates and survival status, and adverse events (AEs) were summarized and evaluated.

To systematically evaluate the response rates, survival status and AEs in the placebo arms of RCTs for HCC.

A systematic search was performed on PubMed, Ovid MEDLINE, Embase and Cochrane Library to identify relevant trials evaluating the efficacy of drugs for the treatment of HCC, published until December 31, 2023. Statistical analysis was performed using R statistical software (version 4.3.2).

A total of 18 RCTs, involving 2390 patients, met the criteria for inclusion in the meta-analysis. The pooled overall disease control rate and objective response rate in the placebo group were 38% [95% confidence interval (CI): 33%-42%] and 1% (95%CI: 1%-2%), respectively. Overall survival and progression-free survival in the placebo group were 7.9 months (95%CI: 7.6-8.31 months) and 1.9 months (95%CI: 1.6-2.1 months), respectively. The incidence of grade 3 or 4 AEs was 37% (95%CI: 30%-43%). Additionally, the incidence of interruptions or dose reductions due to AEs was 20% (95%CI: 13%-27%), while the incidence of treatment discontinuation due to AEs was 9% (95%CI: 6%-12%).

Over one-third of advanced HCC patients exhibit therapy-free disease control, with placebo-arm AEs observed. These findings guide single-arm trials design and enhance patient acceptance of anticancer therapies.