Pharmacometrics Analysis Evaluates Trilaciclib Dosing for Chinese Patients With ES-SCLC

A new study “supports the adoption” of a 240-mg/m² intravenous 3- or 5-day dosing regimen for trilaciclib in Chinese patients with extensive-stage small cell lung cancer (ES-SCLC).

A team from the Shanghai Chest Hospital at the Shanghai Jiao Tong University School of Medicine conducted the pooled pharmacometrics analysis and published their findings in Acta Pharmacologica Sinica. They aimed to analyze “potential ethnic disparities” in the dose–exposure–response relationships of trilaciclib.

Trilaciclib is a first-in-class, intravenous, cyclin-dependent kinase 4/6 inhibitor that was approved in February 2021 by the US Food and Drug Administration to reduce the frequency of chemotherapy-induced bone marrow suppression in adults with ES-SCLC.

The pharmacometrics analysis focused on characterizing dose–exposure–response relationships in patients who were Chinese and those who were not Chinese to “further refine the dosing regimen” for trilaciclib in Chinese patients with ES-SCLC, according to the study authors.

The researchers conducted population pharmacokinetic and exposure–response analyses using pooled data from 4 randomized phase 2/3 trials involving Chinese and non-Chinese patients with ES-SCLC. The population pharmacokinetic analysis showed that trilaciclib clearance was approximately 17% higher in patients who were Chinese than in those who were not Chinese.

“Sex and body surface area influenced trilaciclib pharmacokinetics in both populations but did not exert a significant clinical impact,” the study investigators wrote.

The exposure–response analysis showed that trilaciclib exposure increased with a dosage escalation from 200 to 280 mg/m² without “notable changes” in myeloprotective or antitumor efficacy, according to the study authors. However, the researchers noted that “the incidence of infusion site reactions, headaches, and phlebitis/thrombophlebitis rose with increasing trilaciclib exposure in both Chinese and non-Chinese patients with ES-SCLC.”

The study investigators concluded that “these findings suggest no substantial ethnic disparities in the dose–exposure–response relationship between Chinese and non-Chinese patients,” and that the study data “support the adoption of a 240-mg/m² intravenous 3-day or 5-day dosing regimen for trilaciclib in Chinese patients with ES-SCLC.”

Source: Acta Pharmacologica Sinica