Risk of adverse events in advanced hepatocellular carcinoma with immune checkpoint therapy: A systematic review and meta-analysis

Aims: To evaluate risk of adverse events (AEs) in advanced hepatocellular carcinoma (AHCC) with immune checkpoint therapy in this setting.

Methods: A systematic search of original articles published until November 2019 was performed using PubMed, Embase, Web of Science, and the Cochrane Central Register of Controlled Trials. And a meta-analysis was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement.

Results: A total of eight studies, including 597 patients, met the eligibility criteria. The median cohort size of patients was 75 (range: 18-267). The pooled incidence rates of grade≥3 AEs and fatal adverse events (FAEs) at last follow-up were 20.87 per 100 person-years (95% CI: 11.00-39.59, I²=91.0%) and 4.98 per 100 person-years (95% CI: 1.83-13.56, I²=82.8%). Subgroup analyses showed that pembrolizumab had a lower risk of grade≥3 AEs, but a higher risk of FAEs, when compared with nivolumab and tremelimumab. Meta-regression showed significant correlation between grade≥3 AEs rate and proportion of Child-Pugh A stage. Fatigue (16.9%), adrenal insufficiency (8.5%) and rash (6.8%) were involved in common non-laboratory AEs.

Conclusions: Immune checkpoint therapy significantly increases the risk of AEs in AHCC patients. And the risk of grade≥3 AEs is associated with Child-Pugh classification. Future retrospective analyses and prospective cohort studies are warranted to evaluate the safety of immune checkpoint therapy in AHCC.