This 7-year update of the CROWN trial demonstrated that lorlatinib maintained unprecedented long-term progression-free survival benefit compared to crizotinib in advanced ALK-positive NSCLC, with median PFS not reached after 7 years. Lorlatinib also shows superior and durable intracranial control with no new brain progression events after 30 months, and a manageable safety profile with few treatment-related discontinuations.
Study
|
Randomized, open-label, international, multicenter, phase 3 study [CROWN] |
| Treatment-naive patients with advanced ALK-positive NSCLC |
| Lorlatinib (n=149) vs Crizotinib (n=147)
|
Efficacy
|
Median PFS: NR vs. 9.1 mos (lorlatinib vs. crizotinib) (HR 0.19 [0.13-0.26]) |
| 7-year PFS: 55% vs 3% |
| In patients with baseline brain metastases: median PFS 86.3 mos vs 6.0 mos (HR 0.08 [0.04-0.19])
|
Safety
|
Treatment-related discontinuations: 5% vs 6% |
| Grade 3 or 4 AEs: 77% vs 57% |
| Cardiovascular AEs: 30% vs 29%
|
Ann Oncol. Published online 2026-05
http://doi.org/10.1016/j.annonc.2026.05.692
Reviewed by Ulas D. Bayraktar, MD on Jun 13, 2026
