劳拉替尼治疗ALK阳性晚期非小细胞肺癌的初步疗效和安全性：中国一项二期临床研究

SCI

11 April 2022

Lorlatinib for Previously Treated ALK-Positive Advanced Non-Small Cell Lung Cancer: Primary Efficacy and Safety From a Phase 2 Study in China

（J Thorac Oncol IF：15.609）

• Lu Shun,Zhou Qing,Liu Xiaoqing et al. Lorlatinib for Previously Treated ALK-Positive Advanced Non-Small Cell Lung Cancer: Primary Efficacy and Safety From a Phase 2 Study in China.[J] .J Thorac Oncol, 2022, undefined: undefined.

Introduction 导言

Lorlatinib showed activity in anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC) in a global phase 1/2 study. We report an ongoing phase 2 study in Chinese patients with ALK-positive advanced/metastatic NSCLC.

在一项全球1/2期研究中，劳拉替尼在间变性淋巴瘤激酶(ALK)阳性的非小细胞肺癌(NSCLC)中显示出活性。我们报告了一项正在进行的中国ALK阳性晚期/转移性非小细胞肺癌患者的2期研究。

Methods 方法

Open-label, dual-cohort study (NCT03909971); patients had progressive disease after ALK tyrosine kinase inhibitor (TKI) treatment (Cohort 1: previous crizotinib; Cohort 2: one ALK TKI other than crizotinib [±prior crizotinib]), ≥1 unirradiated extracranial target lesion, ECOG PS of 0-2. Patients received oral lorlatinib 100 mg once-daily in continuous 21-day cycles.

开放标签的双队列研究(NCT03909971)；患者在ALK酪氨酸酶抑制剂治疗后有进展性疾病(队列1：既往使用过克唑替尼；队列2：除克唑替尼外使用过其他ALK TKI[±克唑替尼])，≥1未照射的颅外靶点，ECOG评分0-2。患者口服劳拉替尼100 mg，每天一次，连续21天为一个周期。

Primary endpoint 主要终点

Objective response in Cohort 1 by independent central radiology (ICR) per RECIST version 1.1. Analyses were based on patients receiving ≥1 dose.

根据RECIST版本1.1，队列1的客观反应由独立中心放射学(ICR)完成。分析基于接受≥1剂的患者。

Results 结果

At data cutoff (August 10, 2020), 109 patients were enrolled (Cohort 1: N = 67; Cohort 2: N = 42). Forty-seven patients in Cohort 1 (70.1%; 95% confidence interval [CI]: 57.7-80.7; p < 0.0001; primary endpoint) and 20 patients in Cohort 2 (47.6%; 95% CI: 32.0-63.6; secondary endpoint) achieved objective response by ICR. Median progression-free survival was not reached in Cohort 1 and was 5.6 months in Cohort 2. In patients with brain lesions at baseline, 29/36 patients in Cohort 1 (80.6%; 95% CI: 64.0-91.8) and 10/21 patients in Cohort 2 (47.6%; 95% CI: 25.7-70.2) achieved objective intracranial response by ICR. Hypercholesterolemia (92.7%) and hypertriglyceridemia (90.8%) (cluster terms) were common treatment-related adverse events (TRAEs). Nine patients (8.3%) had serious TRAEs; one permanently discontinued from treatment because of TRAEs.

在数据截止日期(2020年8月10日)，109名患者入选(队列1：67例；队列2：n=42例)。队列1的47名患者(70.1%；95%可信区间：57.7%-80.7；p<0.0001；主要终点)和队列2的20名患者(47.6%；95%可信区间：32.0%-63.6%；次要终点)通过ICR实现了客观反应。队列1未达到中位无进展生存期，队列2为5.6个月。在基线脑部病变患者中，队列1中29/36例(80.6%；95%CI：64.0-91.8)和队列2中10/21例(47.6%；95%CI：25.7-70.2)通过ICR获得了客观的颅内反应。高胆固醇血症(92.7%)和高甘油三酯血症(90.8%)是常见的治疗相关不良事件(TRAE)。9例(8.3%)患者有严重的TRAE，1例因TRAE而永久停止治疗。

Conclusions 结论

Lorlatinib demonstrated a robust and durable response and high intracranial objective response in previously treated Chinese patients with ALK-positive NSCLC.

劳拉替尼在既往治疗的中国ALK阳性非小细胞肺癌患者中表现出强大而持久的反应和较高的颅内客观反应。

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