Hussein Maen, Maglakelidze Marina, Richards Donald A, Sabatini Marielle, Gersten Todd A, Lerro Keith, Sinielnikov Ivan, Spira Alexander, Pritchett Yili, Antal Joyce M, Malik Rajesh, Beck J Thaddeus
Florida Cancer Specialists, Leesburg, FL, USA.
LLC Arensia Exploratory Medicine, Tbilisi, Georgia.
Cancer Manag Res. 2021 Aug 9;13:6207-6218. doi: 10.2147/CMAR.S313045. eCollection 2021.
Trilaciclib is an intravenous cyclin-dependent kinase 4/6 inhibitor indicated to decrease the incidence of chemotherapy-induced myelosuppression (CIM) by protecting hematopoietic stem and progenitor cells and immune system function from chemotherapy-induced damage (myeloprotection). Here, we investigated the myeloprotective effects of trilaciclib among patients at increased risk of CIM.
Data were pooled from three randomized, double-blind, placebo-controlled, phase 2 clinical studies of trilaciclib administered prior to chemotherapy in patients with extensive-stage small cell lung cancer (ES-SCLC). Myeloprotective outcomes were evaluated in patient subgroups based on age (<65 or ≥65 years), risk of chemotherapy-induced febrile neutropenia (FN), and risk of anemia or red blood cell (RBC) transfusions. For the FN and anemia analyses, risk factors were identified from published literature and used to classify patients into FN and anemia risk categories. Subgroup analysis based on age was also performed on patient reported outcome (PRO) measures.
In total, 123 patients received trilaciclib and 119 patients received placebo. Myeloprotective benefits of trilaciclib were observed regardless of age, with greater effects observed among patients aged ≥65 years. Across FN risk factors and categories, trilaciclib had beneficial effects on neutrophil-related endpoints vs placebo, with greater effects observed in patients at higher risk of FN. Effects on RBC-related endpoints favored trilaciclib vs placebo, regardless of anemia risk factors and categories. Improvements in PROs with trilaciclib were observed irrespective of age group, but with greater improvements and less deterioration from baseline observed in older patients.
By both decreasing the incidence of CIM and improving quality of life, trilaciclib has the potential to allow patients receiving chemotherapy for ES-SCLC, including patients who are older or more vulnerable to CIM, to receive chemotherapy on schedule and at standard-of-care doses, and to improve the experience for patients receiving chemotherapy to treat ES-SCLC.
NCT02499770; NCT03041311; NCT02514447.
曲拉西利是一种静脉注射的细胞周期蛋白依赖性激酶4/6抑制剂，旨在通过保护造血干细胞和祖细胞以及免疫系统功能免受化疗诱导的损伤（骨髓保护）来降低化疗诱导的骨髓抑制（CIM）的发生率。在此，我们研究了曲拉西利在CIM风险增加的患者中的骨髓保护作用。
数据来自三项随机、双盲、安慰剂对照的2期临床研究，这些研究在广泛期小细胞肺癌（ES-SCLC）患者化疗前给予曲拉西利。根据年龄（<65岁或≥65岁）、化疗诱导的发热性中性粒细胞减少（FN）风险以及贫血或红细胞（RBC）输血风险对患者亚组的骨髓保护结果进行评估。对于FN和贫血分析，从已发表的文献中确定风险因素，并用于将患者分类为FN和贫血风险类别。还对患者报告结局（PRO）指标进行了基于年龄的亚组分析。
共有123例患者接受曲拉西利，119例患者接受安慰剂。无论年龄如何，均观察到曲拉西利的骨髓保护益处，在≥65岁的患者中观察到更大的效果。在所有FN风险因素和类别中，与安慰剂相比，曲拉西利对中性粒细胞相关终点具有有益作用，在FN风险较高的患者中观察到更大的效果。无论贫血风险因素和类别如何，曲拉西利对RBC相关终点的影响优于安慰剂。无论年龄组如何，均观察到曲拉西利使PRO得到改善，但在老年患者中观察到从基线的改善更大且恶化更少。
通过降低CIM的发生率和改善生活质量，曲拉西利有可能使接受ES-SCLC化疗的患者，包括年龄较大或更易发生CIM的患者，按计划并以标准治疗剂量接受化疗，并改善接受化疗治疗ES-SCLC的患者的体验。
NCT02499770；NCT03041311；NCT02514447。
