1134P - Prevention of hepatic toxicities associated with anaplastic lymphoma kinase inhibitors in the treatment of non-small cell lung cancer by administration of ursodeoxycholic acid: Analysis from the monoinstitutional analysis

Background

ALK gene rearrangement is a driving mutation underlying the development of NSCLC, and has been identified in 5–6% of NSCLC cases. The selective ALK-inhibitors showed therapeutic activity in in patients with non-small cell lung cancer (NSCLC). Hepatotoxicity is reported relatively frequently in clinical practice and may cause either a dose reduction or treatment interruption. Ursodeoxycholic acid, a unique bile acid protects the liver from injury.

Methods

An analysis was performed on two groups of patients: already on treatment with ALK inhibitor and with liver toxicity G1 and G2 (group 1), in prophylaxis at the start of treatment with ALK inhibitor (group 2). Patients were enrolled in the program between February 2018 and February 2022.

Results

Overall, 35 patients with ALK-positive NSCLC gene rearrangement were analyzed in group 1 and 45 patients in group 2. Based on clinical trial experiences, each patient's liver function was assessed at baseline before treatment and monitored every two weeks during the first two months, then monthly. Liver metastases were known in 3 patients in group 1 and 4 patients in group 2 at the time of taking the ALK inhibitor. In group 1 25 patients developed liver toxicity ranging from G1 to G2 and started ursodeoxycholic acid at a dose of 450 mg / day. In group 2 40 patients started treatment with an ALK inhibitor and ursodeoxycholic acid at a dose of 450 mg / day simultaneously. The rate of reduction in liver toxicity from G2 and G1 to G0 was 78% in the evaluable group 1 population (n = 32). In group 2 only 9% of patients developed grade

Conclusions

Alterations in liver enzyme levels are one of the most common problems encountered in everyday clinical practice. In the real world, ursodeoxycholic acid at a dose of 450 mg / day has shown excellent efficacy in the management of liver toxicity associated with ALK inhibitors.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Antonio Lugini.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.