Influence of Hepatic Impairment on Palbociclib Toxicity in Patients With HR+/HER2- Advanced or Metastatic Breast Cancer

Abstract

Objective There is no real-world clinical data available about the relationship between hepatic impairment and palbociclib-induced neutropenia. Hepatic impairment could potentially lead to increased palbociclib exposure which is associated with a lower absolute neutrophil count (ANC). The aim of this study was to assess palbociclib-induced neutropenia in patients with hepatic impairment with locally advanced or metastatic hormone receptor-positive and human epidermal growth factor receptor 2-negative (HR+/HER2-) breast cancer.

Methods CTcue (version 3.10.0) was used to pseudonymously extract patients from the Tergooi Medical Centre who started palbociclib treatment between 1 August 2017 and 1 December 2022. Patients were risk- stratified into groups by hepatic impairment: A (normal): total bilirubin ≤ upper limit of normal (ULN) and alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) ≤ ULN, B1 (mild): total bilirubin ≤ ULN and ALT and/or AST > ULN, B2 (mild): total bilirubin > 1-1.5x ULN and any ALT and/or AST, C (moderate): total bilirubin > 1.5-3x ULN and any ALT and/or AST or D (severe): total bilirubin > 3x ULN and any ALT and/or AST. Primary outcomes were the incidence of and time to neutropenia grade 3 or 4. Secondary outcomes were the incidence of and time to leukopenia and thrombocytopenia grade 3 or 4, dose reductions, elevation of liver enzymes and progression-free survival (PFS). The relationship between neutropenia and PFS was assessed as well.

Results Among 70 included patients, 35 had baseline normal hepatic function and 35 had baseline mild hepatic impairment based on elevated ALT and/or AST. Patients with elevated aminotransferases did not have a higher risk of developing palbociclib-induced neutropenia (relative risk (RR) = 1.10, (95% confidence interval (CI) 0.75 – 1.61, p = 0.626)). The median time to neutropenia was 85 days for patients with normal hepatic function versus 28 days for patients with mild hepatic impairment (p = 0.356) with an adjusted hazard ratio (HR) of 1.77 (95% CI 0.79 – 3.94, p = 0.163). The incidences and time-to-event results regarding the secondary outcomes were not significantly different. Patients who experienced neutropenia showed a longer median survival time compared to patients who did not experience neutropenia (279 days vs. 245 days, p = 0.094).

Conclusions This study shows that patients with baseline elevated ALT and/or AST do not have a significantly higher risk of palbociclib-induced neutropenia than patients with baseline normal hepatic function, nor to develop it sooner. Even though patients with baseline elevated aminotransferases reach their median time to neutropenia earlier, these patients should not be treated differently by clinicians during palbociclib treatment than patients with baseline normal hepatic function.