PD-1 checkpoint inhibitors related immune-mediated hepatitis in colon cancer: A systematic review and meta-analysis.

Abstract

e14615 Background: Immune checkpoint inhibitors have revolutionized the management of advanced colon cancers by targeting programmed death-1 (PD-1) proteins. Along with PD-1, other checkpoint inhibitors PDL-1 and CTL4 have been approved for the treatment of various type of cancers since a decade. However, many immune-related side effects have been associated with them. There is limited data in the literature on PD-1 related hepatotoxicity, mainly immune mediated hepatitis. This systematic review and meta-analysis aim to study the impact of PD-1 checkpoint inhibitors on immune-mediated hepatitis in the context of colon cancer, its incidence among different immunotherapies, risk factors associated with it and exploring treatment modalities. Methods: The study was conducted in accordance with PRISMA guidelines. Multiple databases such as PubMed, EMBASE, Scopus, Cochrane Library and Web of Science from past 10 years were searched up to November 2023. Studies from cohort studies, randomized control trials and case series that have reported on immune-mediated hepatitis in colon cancer patients treated with PD-1 inhibitors were included. Results: Overall pooled incidence of immune mediated hepatitis was between 1% -5% with an average of 4.1% (95% CI, 2.8-5.8) among patients with advanced colon cancer treated with PD-1 inhibitors. Among different inhibitors, incidence was lowest with Pembrolizumab, around 1.4%; and highest with Cemiplimab with 5.1%. This is crucial in optimizing treatment for advanced colon cancers. The meta-analysis also found risk factors of male gender, older age and pre-existing liver-conditions (Hepatitis B and C), contributing to the development of hepatitis. Subgroup analysis will be performed to explore potential differences in incidence rates based on patient characteristics, dosages of medications, duration of treatment and concomitant medications. Other objectives include determining the timeline and grades of toxicity. Conclusions: By incorporating data from other studies and understating safety profiles, the findings will highlight the need for close surveillance for toxicity monitoring. This would also provide insight for clinical providers to make informed decisions regarding treatment selection. Toxicities are noted to be under-reported; hence we urge clinicians to report such immune toxicities. Further research is needed to elucidate underlying mechanisms to develop strategies for mitigating adverse events.