Lorlatinib (ALK TKI) Reaches 55% 7-Year PFS in First-Line ALK+ NSCLC

Lorlatinib is a brain-penetrant third-generation ALK tyrosine kinase inhibitor compared with first-generation ALK/MET/ROS1 inhibitor crizotinib in the Phase 3 CROWN trial for treatment-naïve advanced ALK-positive NSCLC (n=296; NCT03052608). At median follow-up of 83.0 vs 77.2 months, median PFS was not reached with lorlatinib versus 9.1 months with crizotinib (HR 0.19), with 7-year PFS 55% vs 3%; intracranial progression was also sharply reduced, with time to intracranial progression not reached vs 16.4 months (HR 0.06). Safety remained consistent with earlier reports and no treatment-related discontinuations occurred after 26 months; modern ALK comparators such as alectinib in ALEX achieved median PFS around 34.8 months versus crizotinib, so the durability here looks beyond a simple crizotinib-era control effect.