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.