A Rare Event of Liver Dysfunction on Sotorasib and Management Strategy

KRAS mutations are the most common alteration in human cancers, accounting for approximately 30% of mutations in multiple cancer types, including colorectal, pancreatic, non-small lung cancer, and ovarian. Of these, the KRAS p.G12C mutation occurs in 13% of non-small lung cancers and 1% to 3% of colorectal and other cancers (Hong et al., 2020). With the approval of the direct KRAS p.G12C inhibitor sotorasib in early 2021, this first-in-class small-molecule agent has increased progression-free survival by 6.3 months in patients with p.G12C non-small cell lung cancer. Side effects associated with sotorasib have been mild, with the most frequent being diarrhea and nausea, but grade 3 to 4 toxicity has also been observed, which is clinically significant. Grade 3 toxicity related to aspartate aminotransferase and alanine aminotransferase is defined as an increase of more than 5 to 20 times the upper limit of normal (ULN), while grade 4 is more than 20 times the ULN. This is significant and requires withholding treatment as it can be life-threatening in some cases. The following case study outlines a patient who developed abnormal liver enzyme elevation while on the phase I clinical trial of sotorasib, and the management of this event.