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Published on: September 12, 2019
Risk of adverse events in advanced hepatocellular carcinoma with immune checkpoint therapy: A systematic review and
Hang Yuan1, Jiaxi Mao1, Cong Liu1
1Department of Liver Surgery and Organ Transplantation, Naval Medical University, Changzheng Hospital, 415 Fengyang Road, Huangpu District, 200003 Shanghai, PR China.
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.
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