Eribulin, Child-Pugh score, and liver-function tests: lessons from pivotal breast cancer studies 301 and 305

Macpherson, I. R. , He, Y. and Palmieri, C. (2021) Eribulin, Child-Pugh score, and liver-function tests: lessons from pivotal breast cancer studies 301 and 305. Breast Cancer Research, 23, 33. (doi: 10.1186/s13058-021-01407-w) (PMID:33736675) (PMCID:PMC7977154)

Abstract

Background: The recommended starting dose of eribulin in patients with hepatic impairment is based on the Child-Pugh score, largely informed by a pharmacokinetic study of 18 patients. In the pivotal studies of eribulin in metastatic breast cancer (Study 301 and Study 305 [EMBRACE]), entry criteria and dose modifications were based on liver-function test (LFT) results rather than Child-Pugh score. In populations such as patients with metastatic breast cancer, in which metastatic infiltration is the predominant cause of hepatic impairment, using Child-Pugh score may be problematic; in clinical practice, it has been more common for oncologists to make dosing decisions based on LFTs. To address this, the effects of abnormal baseline LFT results on eribulin efficacy and safety were investigated. Methods: In this pooled post hoc analysis, 1062 patients who were randomized to receive eribulin in Studies 301 and 305 were divided into 4 groups: (A) no elevated LFT results (no liver impairment); (B) increased levels of aspartate aminotransferase and/or alanine aminotransferase; (C) decreased albumin and/or increased levels of aspartate aminotransferase and/or alanine aminotransferase but not increased bilirubin; and (D) increased bilirubin. Patients were subcategorized by presence of liver metastasis. Drug exposure, dose intensity, and treatment-emergent adverse events (TEAEs) were analyzed. Results: Eribulin mesylate mean dosage was 0.82 (group A)–0.65 mg/m2/week (group D). Group D had shorter treatment, more dose reductions/delays, more TEAEs leading to dose modifications, and numerically lower objective response rates and clinical benefit rates versus groups A–C. TEAE rates leading to dose modification were similar between group D (45.5%) and groups A–C (range, 43.5–54.9%) in the absence of liver metastases, but higher in group D (91.3%) compared with groups A–C (range, 41.7–54.3%) if liver metastases were present. Conclusions: Mild elevations in bilirubin levels were associated with increased toxicity and a greater requirement for dose modifications. Based both on these study data and existing recommendations, we propose a novel scheme to guide initial dose selection in patients with metastatic breast cancer and hepatic impairment that is based on LFTs rather than Child-Pugh score.

• Item Type: Articles
• Additional Information: This work was supported by Eisai Inc., which funded the provision of medical writing and editorial assistance.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: MacPherson, Professor Iain
• Authors: Macpherson, I. R., He, Y., and Palmieri, C.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Journal Name: Breast Cancer Research
• Publisher: BioMed Central
• ISSN: 1465-5411
• ISSN (Online): 1465-542X
• Copyright Holders: Copyright © 2021 The Authors
• First Published: First published in Breast Cancer Research 23: 33
• Publisher Policy: Reproduced under a Creative Commons License