LBPO.CL01 · 临床研究 · Late-Breaking

洛拉替尼治疗晚期ALK阳性非小细胞肺癌：疗效、安全性及治疗应答预测性生物标志物的探索

Lorlatinib in advanced ALK-positive non-small cell lung cancer: Efficacy, safety and exploration of predictive biomarkers for therapeutic response

编号 LB013 展板 13 时间 4/19 02:00–05:00 区域 Section 50 主讲 Fang Wei, PhD

分会场 Late-Breaking Research: Clinical Research 1

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作者与单位 Authors & Affiliations

Fang Wei¹, Linyan Tian¹, Huiyang Shi¹, Wenxin Jiang¹, Danru Zheng¹, Haiyan Xu², Yan Wang¹

¹Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sci ences and Peking Union Medical College, Beijing, China,²Department of Comprehensive Oncology, National Cancer Center/ National Clinical Research Center for Cancer/ Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China

摘要 Abstract

中文摘要

背景：洛拉替尼已获批作为晚期ALK阳性非小细胞肺癌（NSCLC）的一线治疗；然而，部分患者未能达到最佳应答。本研究旨在探索洛拉替尼在中国晚期ALK阳性NSCLC患者中的真实世界疗效，并识别治疗应答的预测性生物标志物。方法：共纳入2023年6月至2025年10月在中国医学科学院肿瘤医院接受洛拉替尼（100 mg每日一次）治疗的60例晚期ALK阳性NSCLC患者。在基线、治疗后1个月和疾病进展时采集外周血样本。主要终点为客观缓解率（ORR）。结果：一线洛拉替尼实现了87.9%的ORR、100%的疾病控制率（DCR）以及未达到的中位无进展生存期（mPFS）。二线治疗显示ORR为38.5%、DCR为92.3%、mPFS为35.93个月；三线治疗的ORR为33.3%、DCR为100%、mPFS为9.87个月。对于总体人群，ORR为67.3%、DCR为98.2%、mPFS为35.93个月。来自26例患者的配对基线和治疗后1个月血液样本（共51份样本）接受了液相色谱-质谱（LC-MS）脂质代谢组学分析，检测到1077种脂质。经过1个月洛拉替尼治疗后，磷脂酰乙醇胺（PE）和磷脂酰胆碱（PC）上调，而神经酰胺下调。根据最佳总体应答（BOR），患者被分为良好应答（GR，n=20）和有限应答（LR，n=6）组。在GR组中识别出100种差异脂质（尤其是HexCer 18:1;20/24:0，P=0.018），而LR组无显著差异。进一步分析显示，低基线HexCer 18:1;20/24:0表达与更长的PFS相关（P=0.02）。一致地，非进展性疾病（non-PD）患者也具有低基线HexCer 18:1;20/24:0表达（P=0.015），提示其作为预测性生物标志物的潜力。在安全性方面，在可评估安全性的患者中（n=51），所有病例均观察到高脂血症，其中22例患者（43.1%）出现≥III级高脂血症。此外，17例患者（33.3%）出现水肿，8例患者（15.7%）出现肝功能异常，8例患者（15.7%）遭受神经系统不良反应。结论：洛拉替尼在中国晚期ALK阳性NSCLC患者中表现出良好的疗效，总体mPFS为35.93个月，ORR为67.3%，一线mPFS未达到。不良反应可控。低基线HexCer 18:1;20/24:0表达可能作为预测性生物标志物，这需要进一步验证。

查看英文原文 English abstract

Background: Lorlatinib is approved as first-line therapy for advanced ALK-positive non-small cell lung cancer (NSCLC); however, some patients fail to achieve optimal responses. This study aimed to explore the real-world efficacy of lorlatinib in Chinese patients with advanced ALK-positive NSCLC and identify predictive biomarkers for treatment response. Methods: A total of 60 patients with advanced ALK-positive NSCLC treated with lorlatinib (100 mg once daily) at Cancer Hospital of the Chinese Academy of Medical Sciences from June 2023 to October 2025 were enrolled. Peripheral blood samples were collected at baseline, 1 month post-treatment, and at disease progression. The primary endpoint was objective response rate (ORR). Results: First-line lorlatinib achieved an ORR of 87.9%, disease control rate (DCR) of 100%, and unreached median progression-free survival (mPFS). Second-line treatment showed an ORR of 38.5%, DCR of 92.3%, and mPFS of 35.93 months; third-line treatment had an ORR of 33.3%, DCR of 100%, and mPFS of 9.87 months. For the overall population, the ORR was 67.3%, DCR 98.2%, and mPFS 35.93 months. Paired baseline and 1-month post-treatment blood samples from 26 patients (51 samples total) underwent liquid chromatography-mass spectrometry (LC-MS) lipid metabolomics analysis, detecting 1,077 lipid species. After 1 month of lorlatinib treatment, phosphatidylethanolamine (PE) and phosphatidylcholine (PC) were upregulated, while ceramides were downregulated. Based on best overall response (BOR), patients were stratified into the good response (GR, n=20) and limited response (LR, n=6) groups. 100 differential lipid species were identified in the GR group (notably HexCer 18:1;20/24:0, P =0.018), with no significant differences in the LR group. Further analysis showed that low baseline HexCer 18:1;20/24:0 expression correlated with longer PFS ( P =0.02). Consistently, non-progressive disease (non-PD) patients also had low baseline HexCer 18:1;20/24:0 expression ( P =0.015), suggesting its potential as a predictive biomarker. For safety, among the patients evaluable for safety (n=51), hyperlipidemia was observed in all cases, with 22 patients (43.1%) experiencing grade ≥III hyperlipidemia. Additionally, 17 patients (33.3%) had edema, 8 patients (15.7%) had abnormal liver function, and 8 patients (15.7%) suffered from neurological adverse reactions. Conclusions: Lorlatinib exhibits favorable efficacy in Chinese patients with advanced ALK-positive NSCLC, with overall mPFS of 35.93 months, ORR of 67.3%, and unreached first-line mPFS. Adverse reactions were manageable. Low baseline HexCer 18:1;20/24:0 expression may serve as a predictive biomarker, which requires further validation.

利益披露 Disclosure

F. Wei, None.. L. Tian, None.. H. Shi, None.. W. Jiang, None.. D. Zheng, None.. H. Xu, None.. Y. Wang, None.

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