First-Line Lorlatinib Versus Crizotinib in ALK-Positive NSCLC: Japanese Subgroup Analysis of CROWN

Introduction: Lorlatinib, a third-generation ALK inhibitor, was found to have improved efficacy versus crizotinib in patients with previously untreated, advanced ALK-positive NSCLC in the ongoing, global, randomized, phase 3 CROWN study. Methods: The study's primary end point was progression -free survival assessed by blinded independent central re-view. Secondary end points included objective and intracra-nial response. Here, we report efficacy and safety data of the Japanese subgroup of the CROWN study (lorlatinib 100 mg once daily, n = 25; crizotinib 250 mg twice daily, n = 23). Results: Progression-free survival was not reached (95% confidence interval [CI]: 11.3 mo-not reached) for lorlatinib and 11.1 months (95% CI: 5.4-14.8) for crizotinib (hazard ratio = 0.44, 95% CI: 0.19-1.01). Objective response (lor-latinib versus crizotinib) was 68.0% (95% CI: 46.5-85.1) versus 52.2% (95% CI: 30.6-73.2) in all patients, and intracranial response was 100.0% (three of three, 95% CI: 29.2-100.0) versus 28.6% (two of seven; 95% CI: 3.7-71.0) in patients with brain metastases at baseline. The most common adverse events with lorlatinib were hyper-triglyceridemia, hypercholesterolemia, and weight increase; 28.0% and 8.0% of patients had cognitive and mood effects (all grades 1 or 2), respectively. Lorlatinib was associated with more grade 3 or 4 events than crizotinib (80.0% versus 72.7%). Treatment was discontinued owing to adverse events in 16.0% and 27.3% of patients in the lor-latinib and crizotinib groups, respectively. Conclusions: The efficacy and safety of lorlatinib in the Japanese subgroup were similar to those in the CROWN global population, revealing improved outcomes versus crizotinib in Japanese patients with previously untreated, advanced ALK-positive NSCLC. (c) 2023 The Authors. Published by Elsevier Inc. on behalf of the International Association for the Study of Lung Cancer. This is an open access article under the CC BY-NC-ND li-cense (http://creativecommons.org/licenses/by-nc-nd/ 4.0/).