TY - JOUR
T1 - Incidence of hepatotoxicity associated with addition of immune checkpoint blockade to systemic solid tumor therapy
T2 - a meta-analysis of phase 3 randomized controlled trials
AU - Fujiwara, Yu
AU - Horita, Nobuyuki
AU - Harrington, Matthew
AU - Namkoong, Ho
AU - Miyashita, Hirotaka
AU - Galsky, Matthew D.
N1 - Funding Information:
This research was not supported by a specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
Publisher Copyright:
© 2022, The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.
PY - 2022/12
Y1 - 2022/12
N2 - 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: I2 = 11.1%, p for heterogeneity = 0.32, grade 3–5: I2 = 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.
AB - 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: I2 = 11.1%, p for heterogeneity = 0.32, grade 3–5: I2 = 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.
KW - Hepatitis
KW - Hepatotoxicity
KW - Immune checkpoint blockade
KW - Immune checkpoint inhibitor
KW - Immune-related adverse event
KW - Immuno-oncology
UR - http://www.scopus.com/inward/record.url?scp=85128810479&partnerID=8YFLogxK
U2 - 10.1007/s00262-022-03203-7
DO - 10.1007/s00262-022-03203-7
M3 - Review article
C2 - 35471602
AN - SCOPUS:85128810479
SN - 0340-7004
VL - 71
SP - 2837
EP - 2848
JO - Cancer Immunology, Immunotherapy
JF - Cancer Immunology, Immunotherapy
IS - 12
ER -