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Incidence of hepatotoxicity associated with addition of immune checkpoint blockade to systemic solid tumor therapy: a meta-analysis of phase 3 randomized controlled trials. | LitMetric

AI Article Synopsis

  • Hepatotoxicity, a serious side effect that can be life-threatening, is examined in the context of immune checkpoint blockade (ICB) combined with cancer treatments.
  • A systematic review and meta-analysis of 43 randomized controlled trials involving nearly 29,000 cancer patients found that adding ICB significantly raised the incidence of hepatitis and elevated liver enzymes (AST and ALT).
  • The study indicates that regardless of the ICB mechanism used, patients receiving ICB alongside systemic therapy are at a higher risk for liver-related issues, suggesting the need for careful monitoring of liver function during treatment.

Article Abstract

Hepatotoxicity is a major immune-related adverse event that may become life-threatening. The impact of adding immune checkpoint blockade (ICB) to systemic therapy on the incidence of hepatotoxicity remains unknown. We performed a systematic review and meta-analysis to compare the incidence of hepatotoxicity among patients with cancer who received therapy with and without addition of ICB. PubMed, Embase, Web of Science, and Cochrane Library were searched to select phase 3 randomized controlled trials (RCTs) evaluating the effect of adding ICB to systemic therapy, placebo, or supportive care. The odds ratio (OR) of any grade and grade 3-5 hepatitis, elevations in aspartate aminotransferase (AST), and alanine aminotransferase (ALT) was pooled for meta-analysis. 43 RCTs with 28,905 participants were analyzed. Addition of ICB increased the incidence of hepatitis (any grade: OR, 2.13, 95% confidence interval [CI] 1.52-2.97, grade 3-5: OR, 2.66, 95% CI 1.72-4.11), elevated AST (any grade: OR, 2.16, 95% CI 1.73-2.70, grade 3-5: OR, 2.72, 95% CI 1.86-3.99), and elevated ALT (any grade: OR, 2.01, 95% CI 1.59-2.54, grade 3-5: OR, 2.40, 95% CI 1.62-3.55). Subgroup analysis based on the ICB mechanism revealed no significant heterogeneity among each mechanism for hepatitis (any Grade: I = 11.1%, p for heterogeneity = 0.32, grade 3-5: I = 0%, p = 0.48). Adding ICB to systemic therapy increases the incidence of hepatotoxicity regardless of the mechanism of ICB. Hepatotoxicity is common and vigilant monitoring of liver function is required during ICB therapy for patients with cancer.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10992785PMC
http://dx.doi.org/10.1007/s00262-022-03203-7DOI Listing

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