奥希替尼治疗预处理晚期 NSCLC 患者中胚系 BCL2L11 缺失多态性的临床意义。
Clinical implications of germline BCL2L11 deletion polymorphism in pretreated advanced NSCLC patients with osimertinib therapy.
机构信息
Affiliated Tumor Hospital of Xinjiang Medical University, Urumqi, China; Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China.
School of Medicine, Shandong University, Jinan, China.
出版信息
Lung Cancer. 2021 Jan;151:39-43. doi: 10.1016/j.lungcan.2020.12.002. Epub 2020 Dec 3.
INTRODUCTION
B-cell lymphoma 2-like 11 (BCL-2-like 11, BCL2L11, also known as BIM) deletion polymorphism (BIM-del) has been associated with resistance to first-generation epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), and is a poor prognostic factor for EGFR-mutant non-small-cell lung cancer (NSCLC) patients. Nevertheless, the impact of BIM-del in advanced NSCLC patients treated with the third-generation EGFR-TKI osimertinib remains undetermined. This study aims to evaluate the relationship between BIM-del and therapeutic efficacy of osimertinib in pretreated NSCLC patients.
METHODS
Patients subjected to EGFR T790 M detection and prior osimertinib treatment between December 2015 and December 2019 in our hospital were enrolled in this study. Peripheral blood samples from these patients were collected to detect BIM-del by polymerase chain reaction. Cox proportional hazards models were used to analyze the clinical outcomes of patients with and without BIM-del.
RESULTS
In total, 152 Chinese Han NSCLC patients-including 143 T790M-positive and nine T790M-negative patients-were enrolled. BIM-del was detected in only 17.5 % of T790M-positive patients (25/143). The majority of patients were aged <65 years (81.8 %, 117/143), were female (58.7 %, 84/143), were non-smokers (82.5 %, 118/143), had Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1 (88.8 %, 129/143), and exhibited metastases in the central nervous system (CNS) (54.5 %, 78/143). There were no associations between the BIM-del and clinical characteristics (including age, sex, histology, smoking status, stage, ECOG PS score, and CNS metastases). Patients with BIM-del had a poorer objective response rate than those without (28.0 % versus 52.5 %, p = 0.026). Besides, BIM-del was associated with a significantly shorter progression-free survival (PFS) and a moderately shorter overall survival (OS) (8.3 versus 10.5 months, p = 0.031 and 15.9 versus 25.2 months, p = 0.1, respectively). Multivariate analysis indicated that BIM-del was an independent prognostic factor for PFS but not for OS in EGFR T790 M NSCLC patients.
CONCLUSIONS
BIM-del is associated with poor clinical responses and outcomes, and might be a negative predictive and prognostic biomarker in EGFR T790 M NSCLC patients with osimertinib treatment.
简介
B 细胞淋巴瘤 2 样 11（BCL-2-like 11，BCL2L11，也称为 BIM）缺失多态性（BIM-del）与第一代表皮生长因子受体酪氨酸激酶抑制剂（EGFR-TKIs）的耐药性相关，并且是 EGFR 突变型非小细胞肺癌（NSCLC）患者的不良预后因素。然而，第三代 EGFR-TKI 奥希替尼治疗的晚期 NSCLC 患者中 BIM-del 的影响仍不确定。本研究旨在评估 BIM-del 与预处理 NSCLC 患者奥希替尼治疗疗效之间的关系。
方法
本研究纳入了 2015 年 12 月至 2019 年 12 月在我院进行 EGFR T790M 检测和奥希替尼治疗的 NSCLC 患者。收集这些患者的外周血样本，通过聚合酶链反应检测 BIM-del。使用 Cox 比例风险模型分析有和无 BIM-del 的患者的临床结局。
结果
本研究共纳入了 152 例中国汉族 NSCLC 患者，包括 143 例 T790M 阳性和 9 例 T790M 阴性患者。仅在 17.5%（25/143）的 T790M 阳性患者中检测到 BIM-del。大多数患者年龄<65 岁（81.8%，117/143），女性（58.7%，84/143），非吸烟者（82.5%，118/143），东部肿瘤协作组（ECOG）表现状态（PS）0-1（88.8%，129/143），并发生中枢神经系统（CNS）转移（54.5%，78/143）。BIM-del 与临床特征（包括年龄、性别、组织学、吸烟状况、分期、ECOG PS 评分和 CNS 转移）之间无关联。有 BIM-del 的患者客观缓解率低于无 BIM-del 的患者（28.0%与 52.5%，p=0.026）。此外，BIM-del 与较短的无进展生存期（PFS）和较短的总生存期（OS）显著相关（8.3 个月与 10.5 个月，p=0.031 和 15.9 个月与 25.2 个月，p=0.1）。多变量分析表明，BIM-del 是 EGFR T790M NSCLC 患者 PFS 的独立预后因素，但不是 OS 的独立预后因素。
结论
BIM-del 与较差的临床反应和结局相关，并且可能是 EGFR T790M NSCLC 患者接受奥希替尼治疗的阴性预测和预后生物标志物。
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