Original Investigation

Lorlatinib in Tyrosine Kinase Inhibitor−Naive Advanced -Positive Non−Small Cell Lung Cancer

JAMA Oncology 10.1001/jamaoncol.2025.5097

November 26, 2025 at 11:00 AM EST

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What is the efficacy and safety of lorlatinib in -positive non−small cell lung cancer (NSCLC)?This nonrandomized clinical trial of 32 patients found that lorlatinib demonstrated a 73% objective response rate, median progression-free survival of 53.6 months, and overall survival not reached. In patients who were tyrosine kinase inhibitor (TKI)−naive compared with previously treated, objective response rate was 90% vs 60%, and median progression-free survival was not reached vs 35.8 months; grade 3 and 4 adverse effects included hypertriglyceridemia (16%) and hypercholesterolemia (25%), but no treatment-related deaths.Lorlatinib demonstrated durable efficacy and safety in TKI-naive advanced -positive NSCLC, supporting its potential use in earlier lines of therapy.

Corresponding Author: Ji-Youn Han, MD, PhD, Center for Lung Cancer, Division of Hematology and Oncology, Department of Internal Medicine, Research Institute and Hospital, National Cancer Center, 323 Ilsan-ro, Ilsan-dong-gu, Goyang, Republic of Korea (jymama@ncc.re.kr).

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