A case of hepatic dysfunction from crizotinib followed by treatment with entrectinib

Background

Information regarding the safety of entrectinib for previously treated patients and patients with hepatic dysfunction is limited. This is the first case report of treatment modification attributable to hepatic dysfunction caused by crizotinib.

Patients

A 76-year-old Japanese woman was referred to the Department of Respiratory Medicine and Allergy after a computed tomography (CT) scan at the time of thyroid surgery. The CT scan revealed an enlarged right upper lobe nodule. After careful examination, she was diagnosed with T3N2M1c stage IV ROS1-positive lung adenocarcinoma; therefore, crizotinib (500 mg/day) was prescribed. On day 861 of treatment, crizotinib was discontinued because of repeatedly observed increased aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels. Approximately 2 weeks after crizotinib was discontinued, treatment was restarted with entrectinib 600 mg/day.

Conclusions

Entrectinib was prescribed because crizotinib caused hepatic dysfunction; however, the patient experienced grade 3 neutropenia and the creatinine phosphokinase (CPK) levels increased. After the dose reduction, she was able to continue treatment safely, without further worsening of the primary tumor or hepatic dysfunction. Therefore, entrectinib may be an option for patients who need treatment modification because of crizotinib-induced hepatic dysfunction. Increased CPK is a previously unknown adverse event occurring with entrectinib. This information is essential to risk management plans involving this drug. Further information regarding increased CPK and rhabdomyolysis occurring in patients treated with entrectinib is needed.