Final Overall Survival and Long-Term Safety of Lorlatinib in Patients With ALK-Positive NSCLC From the Pivotal Phase 2 Study: A Brief Report
Year: 2024
Type: article
Study design: Clinical Trial
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.
Source: Journal of Thoracic Oncology
Institutions: University of California, Irvine, UC Irvine Chao Family Comprehensive Cancer Center, Peter MacCallum Cancer Centre, Université Paris-Sud, Institut Gustave Roussy, Centro di Riferimento Oncologico, National Taiwan University Hospital, Azienda Ospedaliera di Perugia, University of Colorado Cancer Center, Massachusetts General Hospital, Pfizer (Italy), National University Cancer Institute, Singapore, National University Health System
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $4,000
Funder: Pfizer
OpenAlex ID: W4404625339