1. Lorlatinib for Previously Treated ALK-Positive Advanced NSCLC: Primary Efficacy and Safety From a Phase 2 Study in People's Republic of China.
- Author
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Lu S, Zhou Q, Liu X, Du Y, Fan Y, Cheng Y, Fang J, Lu Y, Huang C, Zhou J, Song Y, Wang K, Pan H, Yang N, Li J, Chen G, Chang J, Cui J, Liu Z, Bai C, Zhang H, Zhao H, Zhang K, Peltz G, Li H, and Wu YL
- Subjects
- Aminopyridines adverse effects, Cohort Studies, Crizotinib therapeutic use, Humans, Lactams adverse effects, Protein Kinase Inhibitors adverse effects, Pyrazoles adverse effects, Receptor Protein-Tyrosine Kinases, Taiwan, Carcinoma, Non-Small-Cell Lung drug therapy, Carcinoma, Non-Small-Cell Lung pathology, Lung Neoplasms drug therapy, Lung Neoplasms pathology
- Abstract
Introduction: Lorlatinib was found to have activity in ALK-positive NSCLC in a global phase 1 and 2 study. We report an ongoing phase 2 study in Chinese patients with ALK-positive 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., (Copyright © 2022 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)
- Published
- 2022
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