Trilaciclib: A First-in-class Therapy to Reduce Chemotherapy-induced Myelosuppression

J. Young, A. Tan
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Abstract

Oral cyclin-dependent kinase (CDK) 4/6 inhibitors are routinely used to treat metastatic hormone receptor-positive human epidermal growth factor receptor 2-negative breast cancer in combination with endocrine therapy; however, they have not been widely used for other tumour types. Trilaciclib is an intravenous CDK 4/6 inhibitor that causes reversible cell cycle arrest in the G1 phase and transient haematopoietic stem and progenitor cell arrest. Ultimately, this protects the bone marrow and immune system from the cytotoxic impact of chemotherapy. Trilaciclib has been evaluated in extensive-stage small cell lung cancer in combination with chemotherapy as a myeloprotective agent and was approved by the US Food and Drug Administration for this use in February 2021. In metastatic triple-negative breast cancer, trilaciclib plus chemotherapy had a survival benefit over chemotherapy alone. This is being further investigated in a phase III trial. This review outlines the mechanism of this novel agent and describes preclinical and clinical data, characterizing its use in extensive-stage small cell lung cancer and advanced triple-negative breast cancer.
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Trilaciclib:减少化疗诱导的骨髓抑制的一流疗法
口服细胞周期蛋白依赖性激酶(CDK) 4/6抑制剂常规用于治疗转移激素受体阳性的人表皮生长因子受体2阴性乳腺癌联合内分泌治疗;然而,它们尚未广泛用于其他类型的肿瘤。Trilaciclib是一种静脉注射cdk4 /6抑制剂,可导致可逆的细胞周期阻滞在G1期和短暂的造血干细胞和祖细胞阻滞。最终,这可以保护骨髓和免疫系统免受化疗的细胞毒性影响。Trilaciclib已被评估为广泛期小细胞肺癌联合化疗的骨髓保护剂,并于2021年2月获得美国食品和药物管理局(fda)的批准。在转移性三阴性乳腺癌中,trilaciclib加化疗比单独化疗更有利于生存。目前正在III期临床试验中进行进一步研究。本文概述了这种新型药物的作用机制,描述了临床前和临床数据,描述了其在大分期小细胞肺癌和晚期三阴性乳腺癌中的应用。
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