Abstract
Ribociclib adds progression-free survival and overall survival benefit in combination with endocrine therapy for first-line treatment of advanced HR+ HER2- breast cancer; however, it comes with a risk of hepatotoxicity. There is guidance for monitoring liver function and holding the medication if hepatotoxicity arises. However, there is minimal guidance for management if withholding the medication alone is insufficient. We present a case of a woman with de novo metastatic HR+ HER2- breast cancer who developed grade 2 AST and ALT elevation after two cycles of ribociclib and anastrozole, which progressed over several weeks to Grade 4 hepatotoxicity despite holding the medication. Extensive evaluation revealed drug-induced liver injury from ribociclib as the cause. Ultimately, a long course of corticosteroids was initiated with remarkable response and resolution of transaminitis. An empiric trial of corticosteroids should be considered for patients with severe ongoing hepatotoxicity from CDK4/6 inhibitors despite cessation of the drug.