Effect of Hepatic Impairment on Trilaciclib Pharmacokinetics

Abstract

AbstractTrilaciclib is a first‐in‐class, intravenous cyclin‐dependent kinase 4 and 6 inhibitor approved for reducing the incidence of chemotherapy‐induced myelosuppression in adult patients with extensive‐stage small cell lung cancer receiving a platinum/etoposide‐containing or topotecan‐containing regimen. No dose adjustment is recommended for participants with mild hepatic impairment (HI) based on previous population pharmacokinetic (PK) analysis. This open‐label, parallel‐group study examined the impact of moderate and severe HI on the PK of trilaciclib. The study employed a reduced study design. Participants with moderate (Child–Pugh B, n = 8) and severe (Child–Pugh C, n = 5) HI and matched healthy controls (n = 11) received a single intravenous dose of trilaciclib 100 mg/m2. The unbound fraction of trilaciclib was comparable between the HI groups and the matched healthy control group. The unbound trilaciclib extent of exposure (i.e., area under the concentration‐time curve) in participants with moderate and severe HI was ∼40% and ∼60% higher, respectively, compared with healthy matched controls based on Child–Pugh classification. Ad hoc analysis using National Cancer Institute classification showed similar results. The US Food and Drug Administration‐approved trilaciclib dose of 240 mg/m2 should be reduced by ∼30%, to 170 mg/m2, for patients with moderate or severe HI.