Wang Jing, Zhao Yizhuo, Wang Qiming, Zhang Li, Shi Jianhua, Wang Zhehai, Cheng Ying, He Jianxing, Shi Yuankai, Yu Hao, Zhao Yang, Chen Weiqiang, Luo Yi, Wang Xiuwen, Nan Kejun, Jin Faguang, Dong Jian, Li Baolan, Liu Zhujun, Han Baohui, Li Kai
Department of Pulmonary Oncology, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, China.
Department of Respiratory Medicine, Shanghai Chest Hospital, Shanghai 230030, China.
Cancer Biol Med. 2018 Nov;15(4):443-451. doi: 10.20892/j.issn.2095-3941.2018.0158.
Anlotinib hydrochloride is a multitarget tyrosine kinase inhibitor that targets vascular endothelial growth factor receptor, fibroblast growth factor receptor, platelet-derived growth factor receptor, c-Kit, and c-MET; therefore, it exhibits both antitumor and anti-angiogenetic activities. A phase III trial has shown that anlotinib improved progression-free survival (PFS) and overall survival (OS) in patients with advanced non-small cell lung cancer (NSCLC), who presented with progressive disease or intolerance after standard chemotherapy. This study aimed to analyze the characteristics of patients receiving anlotinib treatment to determine the dominant populations who are fit for the treatment.
Data were collected from March 2015 to January 2017 from a randomized, double-blind, placebo-controlled, multicenter, phase III trial of anlotinib (ALTER0303). A total of 437 patients were enrolled and randomly allocated (2:1) to the anlotinib and placebo groups. Kaplan-Meier analysis and log-rank test were performed to compare PFS and OS. Cox proportional hazards model was adopted for multivariate prognostic analysis.
Multivariate analysis indicated that high post-therapeutic peripheral blood granulocyte/lymphocyte ratio and elevated alkaline phosphatase levels were independent risk factors for PFS. Meanwhile, elevated thyroid-stimulating hormone, blood glucose, and triglyceride levels; hypertension; and hand-foot syndrome were independent protective factors of PFS. High post-therapeutic peripheral blood granulocyte/lymphocyte ratio, an Eastern Cooperative Oncology Group (ECOG) score ≥ 2, and the sum of the maximal target lesion length at baseline were independent risk factors of OS, and hypertriglyceridemia was an independent protective factor of OS.
This study preliminarily explored the possible factors that affected PFS and OS after anlotinib treatment in patients with advanced refractory NSCLC, and the baseline characteristics of the therapeutically dominant populations were then identified.
盐酸安罗替尼是一种多靶点酪氨酸激酶抑制剂，可作用于血管内皮生长因子受体、成纤维细胞生长因子受体、血小板衍生生长因子受体、c-Kit和c-MET；因此，它具有抗肿瘤和抗血管生成活性。一项III期试验表明，安罗替尼可改善晚期非小细胞肺癌（NSCLC）患者的无进展生存期（PFS）和总生存期（OS），这些患者在标准化疗后出现疾病进展或不耐受。本研究旨在分析接受安罗替尼治疗患者的特征，以确定适合该治疗的主要人群。
数据收集自2015年3月至2017年1月进行的一项安罗替尼（ALTER0303）随机、双盲、安慰剂对照、多中心III期试验。共纳入437例患者，并随机（2:1）分配至安罗替尼组和安慰剂组。采用Kaplan-Meier分析和对数秩检验比较PFS和OS。采用Cox比例风险模型进行多因素预后分析。
多因素分析表明，治疗后外周血粒细胞/淋巴细胞比值高和碱性磷酸酶水平升高是PFS的独立危险因素。同时，促甲状腺激素、血糖和甘油三酯水平升高；高血压；以及手足综合征是PFS的独立保护因素。治疗后外周血粒细胞/淋巴细胞比值高、东部肿瘤协作组（ECOG）评分≥2以及基线时最大靶病灶长度之和是OS的独立危险因素，高甘油三酯血症是OS的独立保护因素。
本研究初步探讨了影响晚期难治性NSCLC患者接受安罗替尼治疗后PFS和OS的可能因素，并确定了治疗主要人群的基线特征。
