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Severe Immune Checkpoint Inhibitor Hepatitis in KRAS G12C-Mutant NSCLC Potentially Triggered by Sotorasib: Case Report

Parvin Begum, Robert Goldin, Lucia Possamai, Sanjay Popat

2021JTO Clinical and Research Reports45 citationsDOIOpen Access PDF

Abstract

Sotorasib is a first-in-class small molecule that irreversibly inhibits KRAS G12C, locking it in an inactive state, inhibiting oncogenic signaling, and inducing a proinflammatory microenvironment. Here, we report the first case of life-threatening hepatitis in a patient with NSCLC shortly after commencing sotorasib, in which biopsy result was consistent with checkpoint inhibitor (CPI) immune-related adverse event, implicating sotorasib as being able to trigger CPI immune hepatitis. Given the large proportion of patients potentially treatable with sequential sotorasib after CPI, coupled with limited trial data, sotorasib-triggered CPI immune-related hepatitis should be considered in patients with sotorasib hepatotoxicity.

Topics & Concepts

KRASImmune systemMedicineHepatitisCancer researchProinflammatory cytokineAdverse effectImmunologyInternal medicineCancerInflammationColorectal cancerChronic Lymphocytic Leukemia ResearchCancer Immunotherapy and BiomarkersPI3K/AKT/mTOR signaling in cancer
Severe Immune Checkpoint Inhibitor Hepatitis in KRAS G12C-Mutant NSCLC Potentially Triggered by Sotorasib: Case Report | Litcius