Treatment-related adverse events of first-line immunotherapy versus sorafenib for advanced hepatocellular carcinoma: a meta-analysis

BackgroundDespite all the improvements achieved over the last decade, the use of immune checkpoint inhibitors (ICIs) has been associated to a wide range of adverse drug events, which are frequently markedly different from those observed with cytotoxic chemotherapy and targeted therapies, such as sorafenib.Research design and methodsWe performed a meta-analysis with the aim to compare grade 3/4 treatment-related adverse events (TRAEs), grade 5 TRAEs, serious TRAEs, and TRAEs leading to discontinuation in ICIs versus sorafenib across phase III clinical trials of first-line treatment for advanced hepatocellular carcinoma (HCC).ResultsOdds ratios (ORs) with 95% confidence intervals (CIs) were calculated. Patients treated with ICIs showed higher risk of serious TRAEs (OR 1.48, 95% CI = 1.16-1.9) while sorafenib treatment was associated with higher risk of TRAEs leading to discontinuation (OR 0.65, 95% CI = 0.48-0.89). No differences in grade 3/4 TRAEs and grade 5 TRAEs.ConclusionsBeyond activity and efficacy, careful consideration should be given to toxicity while choosing the appropriate first-line treatment in HCC.

Automated summary

Despite improvements, immune checkpoint inhibitors (ICIs) have been associated with a wide range of adverse drug events in advanced hepatocellular carcinoma (HCC) treatment. A meta-analysis comparing ICIs and sorafenib in phase III clinical trials showed that ICIs had a higher risk of serious TRAEs, while sorafenib had a higher risk of TRAEs leading to discontinuation. No differences were observed in grade 3/4 TRAEs and grade 5 TRAEs. Careful consideration of toxicity is important in choosing the appropriate first-line treatment for HCC.