INTRODUCTION: Lorlatinib, a third-generation anaplastic lymphoma kinase (ALK) inhibitor, showed significantly longer progression-free survival (PFS) than crizotinib in the phase 3 CROWN trial (NCT03052608) in patients with previously untreated advanced ALK-positive non-small cell lung cancer (NSCLC). Efficacy was similar in the Asian subgroup. We present an updated subgroup analysis in Asian patients after 5 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)
5-year PFS was 63% (95% CI: 49-74) and 7% (95% CI: 2-17). Objective response rate (ORR) was 81% (95% CI: 69-90) with lorlatinib and 59% (95% CI: 46‒71) with crizotinib. In patients with baseline brain metastases, intracranial (IC) ORR was 69% (95% CI: 39‒91) with lorlatinib and 6% (95% CI: <
1‒30) with crizotinib. Median time to IC 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 5 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.