Abstract：
This study aimed to analyze potential ethnic disparities in the dose-exposure-response relationships of trilaciclib, a first-in-class intravenous cyclin-dependent kinase 4/6 inhibitor for treating chemotherapy-induced myelosuppression in patients with extensive-stage small cell lung cancer (ES-SCLC). This investigation focused on characterizing these relationships in both Chinese and non-Chinese patients to further refine the dosing regimen for trilaciclib in Chinese patients with ES-SCLC. Population pharmacokinetic (PopPK) and exposure-response (E-R) analyses were conducted using pooled data from four randomized phase 2/3 trials involving Chinese and non-Chinese patients with ES-SCLC. PopPK analysis revealed that trilaciclib clearance in Chinese patients was approximately 17% higher than that in non-Chinese patients with ES-SCLC. Sex and body surface area influenced trilaciclib pharmacokinetics in both populations but did not exert a significant clinical impact. E-R analysis demonstrated that trilaciclib exposure increased with a dosage escalation from 200 to 280 mg/m2, without notable changes in myeloprotective or antitumor efficacy. However, 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. These findings suggest no substantial ethnic disparities in the dose-exposure-response relationship between Chinese and non-Chinese patients. They support the adoption of a 240-mg/m2 intravenous 3-day or 5-day dosing regimen for trilaciclib in Chinese patients with ES-SCLC.
摘要：
本研究旨在分析trilaciclib的剂量-暴露-反应关系中潜在的种族差异，一类静脉内细胞周期蛋白依赖性激酶4/6抑制剂,用于治疗广泛期小细胞肺癌(ES-SCLC)患者化疗诱导的骨髓抑制.这项研究的重点是在中国和非中国患者中描述这些关系，以进一步完善中国ES-SCLC患者中trilaciclib的给药方案。人群药代动力学（PopPK）和暴露反应（E-R）分析使用来自四个随机2/3期试验的汇总数据进行，涉及中国和非中国ES-SCLC患者。PopPK分析显示，中国患者的trilaciclib清除率比非中国ES-SCLC患者高出约17％。性别和体表面积影响了这两个人群的trilaciclib药代动力学，但未产生明显的临床影响。E-R分析表明，随着剂量从200mg/m2增加到280mg/m2，trilaciclib暴露量增加，骨髓保护或抗肿瘤功效没有显着变化。然而,输液部位反应的发生率，头痛,在中国和非中国患有ES-SCLC的患者中,静脉炎/血栓性静脉炎随着三拉西尼暴露量的增加而增加。这些发现表明，中国和非中国患者之间的剂量-暴露-反应关系没有实质性的种族差异。他们支持在中国ES-SCLC患者中采用240-mg/m2静脉内3天或5天的三拉西尼给药方案。
