Lorlatinib for Previously Treated ALK-Positive Advanced NSCLC: Primary Efficacy and Safety From a Phase 2 Study in People's Republic of China

作者：Lu, Shun; Zhou, Qing; Liu, Xiaoqing; Du, Yingying; Fan, Yun; Cheng, Ying; Fang, Jian; Lu, You; Huang, Cheng; Zhou, Jianying; Song, Yong; Wang, Kai; Pan, Hongming; Yang, Nong; Li, Juan; Chen, Gongyan; Chang, Jianhua; Cui, Jiuwei; Liu, Zhe; Bai, Chunxue; Zhang, Helong; Zhao, Huadong; Zhang, Kaiting; Peltz, Gerson; Li, Heyan; Wu, Yi-Long^*

来源：Journal of Thoracic Oncology, 2022, 17(6): 816-826.

DOI：10.1016/j.jtho.2022.02.014

• Lorlatinib
• ALK
• Tyrosine kinase inhibitor
• Non-small cell lung cancer
• China

Introduction: Lorlatinib was found to have activity in ALKpositive NSCLC in a global phase 1 and 2 study. We report an ongoing phase 2 study in Chinese patients with ALKpositive advanced or metastatic NSCLC. @@@ Methods: Open-label, dual-cohort study (NCT03909971); patients had progressive disease after ALK tyrosine kinase inhibitor treatment (cohort 1: previous crizotinib; cohort 2: one ALK tyrosine kinase inhibitor other than crizotinib [+/- prior crizotinib]), more than or equal to one unirradiated extracranial target lesion, and Eastern Cooperative Oncology Group performance status of 0 to 2. Patients received oral lorlatinib 100 mg once daily in continuous 21-day cycles. Primary end point: objective response in cohort 1 by independent central radiology (ICR) according to Response Evaluation Criteria in Solid Tumors version 1.1. Analyses were based on patients receiving more than or equal to one dose. @@@ Results: At data cutoff (August 10, 2020), 109 patients were enrolled (cohort 1: n = 67; cohort 2: n = 42). A total of 47 patients in cohort 1 (70.1%, 95% confidence interval [CI]: 57.7-80.7, p < 0.0001; primary end point) and 20 patients in cohort 2 (47.6%, 95% CI: 32.0-63.6, secondary end point) 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 of 36 patients in cohort 1 (80.6%, 95% CI: 64.0-91.8) and 10 of 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. @@@ Conclusions: Lorlatinib was found to have a robust and durable response and high intracranial objective response in previously treated Chinese patients with ALK-positive NSCLC.

• 单位
  1; 哈尔滨医科大学; 四川大学; 复旦大学; 中国人民解放军第四军医大学; 5; 吉林大学; 广东省人民医院; 安徽医科大学; 浙江大学; 中国医学科学院