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. 2016 Sep 28:10:3153-3161.
doi: 10.2147/DDDT.S115493. eCollection 2016.

Incidence and risk of hepatic toxicities with PD-1 inhibitors in cancer patients: a meta-analysis

Xi Zhang  1 , Yuge Ran  1 , Kunjie Wang  2 , Yuanxue Zhu  2 , Jinghua Li  3
Affiliations

Incidence and risk of hepatic toxicities with PD-1 inhibitors in cancer patients: a meta-analysis

Xi Zhang et al. Drug Des Devel Ther. .

Abstract

Purpose: Anti-programmed cell death receptor-1 (PD-1) antibodies have demonstrated antitumor activity in many cancer entities. Hepatic adverse events (AEs) are one of its major side effects, but the overall risks have not been systematically evaluated. Thus, we conducted this meta-analysis to investigate the overall incidence and risk of developing hepatic AEs in cancer patients treated with PD-1 inhibitors.

Methods: PubMed, Embase, and oncology conference proceedings were searched for relevant studies. Eligible studies were randomized controlled trials of cancer patients treated with PD-1 inhibitors with adequate data on hepatic AEs.

Results: A total of nine randomized controlled trials with a variety of solid tumors were eligible for the meta-analysis. The use of PD-1 inhibitors significantly increased the risk of developing all-grade hepatic AEs but not for high-grade hepatic AEs in comparison with chemotherapy or everolimus control. Additionally, the risk of all-grade and high-grade hepatic AEs with a nivolumab/ipilimumab combination was substantially higher than ipilimumab. No significant differences in the risk of all-grade and high-grade hepatic AEs were found between PD-1 inhibitors monotherapy and ipilimumab.

Conclusion: While the use of PD-1 inhibitors is associated with an increased risk of developing hepatic AEs in cancer patients, this is primarily for lower grade events.

Keywords: PD-1 inhibitors; cancer; hepatic toxicities; meta-analysis.

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Figures

Figure 1
Figure 1
Flow chart of selection process for trials included in meta-analysis. Abbreviations: AEs, adverse events; RCTs, randomized controlled trials.
Figure 2
Figure 2
Forest plot for meta-analysis of incidence of all-grade elevated ALT (A) and AST (B) and high-grade elevated ALT (C) and AST (D). Abbreviations: ALT, alanine aminotransferase; AST, aspartate aminotransferase; CI, confidence interval.
Figure 3
Figure 3
RR of all-grade elevated ALT (A) and AST (B) and high-grade elevated ALT (C) and AST (D) for cancer patients receiving PD-1 inhibitors monotherapy compared with control. Abbreviations: ALT, alanine aminotransferase; AST, aspartate aminotransferase; PD-1, program death 1; CI, confidence interval; RR, risk ratio.
Figure 4
Figure 4
Relative risk of all-grade elevated ALT (A) and AST (B) and high-grade elevated ALT (C) and AST (D) for cancer patients receiving a nivolumab/ipilimumab combination compared with ipilimumab control. Abbreviations: ALT, alanine aminotransferase; AST, aspartate aminotransferase; PD-1, program death 1; CI, confidence interval.
Figure 5
Figure 5
Relative risk of all-grade elevated ALT (A) and AST (B) and high-grade elevated ALT (C) and AST (D) for cancer patients receiving PD-1 inhibitors monotherapy compared with ipilimumab control. Abbreviations: ALT, alanine aminotransferase; AST, aspartate aminotransferase; PD-1, program death 1; CI, confidence interval.
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References

    1. Postow MA, Callahan MK, Wolchok JD. Immune checkpoint blockade in cancer therapy. J Clin Oncol. 2015;33(17):1974–1982. - PMC - PubMed
    1. Taube JM, Klein A, Brahmer JR, et al. Association of PD-1, PD-1 ligands, and other features of the tumor immune microenvironment with response to anti-PD-1 therapy. Clin Cancer Res. 2014;20(19):5064–5074. - PMC - PubMed
    1. Zou W, Chen L. Inhibitory B7-family molecules in the tumour microenvironment. Nat Rev Immunol. 2008;8(6):467–477. - PubMed
    1. Ansell SM, Lesokhin AM, Borrello I, et al. PD-1 blockade with nivolumab in relapsed or refractory Hodgkin’s lymphoma. N Engl J Med. 2015;372(4):311–319. - PMC - PubMed
    1. Herbst RS, Baas P, Kim DW, et al. Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): a randomised controlled trial. Lancet. 2016;387(10027):1540–1550. - PubMed