First-Line Lorlatinib Versus Crizotinib in Asian Patients With Advanced ALK-Positive NSCLC: Five-Year Outcomes From the CROWN Study

Abstract

Introduction: Lorlatinib, a third-generation anaplastic lymphoma kinase inhibitor, reported significantly longer progression-free survival (PFS) than crizotinib in the phase 3 CROWN trial (NCT03052608) in patients with previously untreated advanced anaplastic lymphoma kinase-positive NSCLC. Efficacy was similar in the Asian subgroup. We present an updated subgroup analysis in Asian patients after five years of follow-up. Methods: Patients were randomly (1:1) assigned to receive lorlatinib 100 mg once daily (n = 59) or crizotinib 250 mg twice daily (n = 61). This post hoc analysis presents updated investigator-assessed efficacy outcomes, safety, and biomarker analyses. Results: After a median follow-up of 62.4 months for lorlatinib and 55.1 months for crizotinib, median PFS was not reached (NR, 95% confidence interval [CI]: 64.3-NR) and 9.2 months (95% CI: 7.2-12.7), respectively (hazard ratio [HR] = 0.22, 95% CI: 0.13-0.37); the five-year PFS was 63% (95% CI: 49-74) and 7% (95% CI: 2-17). The objective response rate was 81% (95% CI: 69-90) with lorlatinib and 59% (95% CI: 46-71) with crizotinib. In patients with baseline brain metastases, the intracranial objective response rate was 69% (95% CI: 39-91) with lorlatinib and 6% (95% CI: <1-30) with crizotinib. The median time to intracranial progression was NR (95% CI: NR-NR) and 14.6 months (95% CI: 9.2-27.4), respectively (HR = 0.01, 95% CI: <0.01-0.11). Safety profiles were consistent with the entire population. Conclusions: After five years of follow-up, lorlatinib efficacy and safety in the Asian subgroup of CROWN continue to be consistent with those in the overall population, with PFS remaining unreached with lorlatinib. (c) 2025 The Author(s). Published by Elsevier Inc. on behalf of International Association for the Study of Lung Cancer. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).