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

Parvin Begum; Robert D Goldin; Lucia A Possamai; Sanjay Popat

doi:10.1016/j.jtocrr.2021.100213

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

JTO Clin Res Rep. 2021 Aug 2;2(9):100213. doi: 10.1016/j.jtocrr.2021.100213. eCollection 2021 Sep.

Authors

Parvin Begum¹, Robert D Goldin², Lucia A Possamai², Sanjay Popat^{1

3}

Affiliations

¹ Lung Unit, Royal Marsden NHS Foundation Trust, London, United Kingdom.
² Department of Metabolism, Digestion & Reproduction, Imperial College London, London, United Kingdom.
³ Thoracic Oncology, The Institute of Cancer Research, London, United Kingdom.

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.

Keywords: Autoimmune hepatitis; Case report; Immune checkpoint inhibitor; KRAS G12C; Sotorasib.

Publication types

Case Reports