Final Overall Survival and Long-Term Safety of Lorlatinib in Patients With ALK-Positive NSCLC From the Pivotal Phase 2 Study: A Brief Report

Ou, SI; Solomon, BJ; Besse, B; Bearz, A; Lin, CC; Chiari, R; Camidge, DR; Lin, JJ; Abbattista, A; Toffalorio, F; Soo, RA

Author(s): Ou, SI; Solomon, BJ; Besse, B; Bearz, A; Lin, CC; Chiari, R; Camidge, DR; Lin, JJ; Abbattista, A; Toffalorio, F; Soo, RA;
Details: Publication Year 2025-04,Volume 20,Issue #4,Page 513-520
Journal Title: Journal of Thoracic Oncology
Publication Type: Research article
Abstract: INTRODUCTION: Lorlatinib is a potent, brain-penetrant, third-generation inhibitor of anaplastic lymphoma kinase (ALK) and ROS1 tyrosine kinases with broad coverage of ALK resistance mutations. We present the overall survival (OS) and long-term safety of lorlatinib in patients with advanced ALK-positive NSCLC from the final analyses of the pivotal phase 2 study. METHODS: Adults with ALK-positive NSCLC, enrolled in expansion cohorts (EXPs) on the basis of prior therapy (EXP1-5), received lorlatinib 100 mg orally once daily in continuous 21-day cycles. The primary endpoint was the objective response rate; secondary endpoints included OS and safety. RESULTS: Thirty patients were enrolled in EXP1 (treatment naïve), 59 in EXP2-3A (disease progression after crizotinib ± chemotherapy), 28 in EXP3B (disease progression after one second-generation ALK tyrosine kinase inhibitor [TKI] ± chemotherapy), 111 in EXP4-5 (disease progression after ≥2 ALK TKIs ± chemotherapy), and 139 in EXP3B-5 (disease progression after ≥1 ALK TKI ± chemotherapy). Median OS was not reached (NR) (95% confidence interval [CI]: NR-NR) in EXP1, NR (95% CI: 51.5-NR) in EXP2-3A, 37.4 months (95% CI: 12.3-NR) in EXP3B, 19.2 months (95% CI: 15.4-30.2) in EXP4-5, and 20.7 months (95% CI: 16.1-30.3) in EXP3B-5. All-cause adverse events leading to dose reduction were reported in 77 patients (28%), temporary treatment discontinuation in 158 patients (57%), and permanent discontinuation in 35 patients (13%). CONCLUSIONS: After a minimum follow-up of five years, final analyses from the global phase 2 study confirmed substantial activity, prolonged OS, and generally consistent safety findings with lorlatinib in treatment-naïve and previously treated patients with ALK-positive NSCLC. CLINICALTRIALS: gov NCT01970865.
Publisher: Elsevier
Keywords: Humans; Male; Female; *Carcinoma, Non-Small-Cell Lung/drug therapy/pathology/mortality; *Lung Neoplasms/drug therapy/pathology/mortality; Middle Aged; *Anaplastic Lymphoma Kinase/metabolism; *Lactams/therapeutic use; Aminopyridines; Aged; Adult; *Lactams, Macrocyclic/therapeutic use; Survival Rate; Follow-Up Studies; Protein Kinase Inhibitors/therapeutic use; Prognosis; Pyrazoles; ALK tyrosine kinase inhibitor; long-term safety; lorlatinib; non-small cell lung cancer; overall survival
Department(s): Medical Oncology
Publisher's Version: https://doi.org/10.1016/j.jtho.2024.11.021
Open Access at Publisher's Site: https://doi.org/10.1016/j.jtho.2024.11.021
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2024-12-12 03:22:39

Last Modified: 2025-05-15 04:17:35