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CROWN — Lorlatinib vs crizotinib, 1L advanced ALK+ NSCLC (7-year update)

Abstract: 8502 · Session: Lung Cancer — Non-Small Cell Metastatic, Oral Abstract Session, Fri May 29, 2026 · Presenter: Tony S. K. Mok, MD (Chinese University of Hong Kong) · Embargo: May 29, 2026

At a glance

  • Sponsor: Pfizer Inc.
  • PI / presenter: Tony S. K. Mok, MD — Chinese University of Hong Kong, Dept. of Clinical Oncology
  • NCT ID: NCT03052608
  • Phase: 3
  • Design: Randomized, open-label, 1:1 lorlatinib vs crizotinib; previously untreated advanced/metastatic ALK+ NSCLC. This is the 7-year (longest follow-up) update, an unplanned post-hoc analysis prompted by median PFS still being unreached at the 3- and 5-year marks; simultaneous publication in Annals of Oncology.
  • N: 296 (lorlatinib n=149; crizotinib n=147)
  • Primary endpoint(s): Progression-free survival (blinded independent central review at primary analysis; investigator-assessed PFS reported in long-term updates)
  • Comparator: Crizotinib (XALKORI)
  • Indication: Advanced / metastatic ALK-positive NSCLC
  • Line: First-line (1L)

Headline result

At a median follow-up of 83.0 months (lorlatinib) vs 77.2 months (crizotinib), investigator-assessed median PFS remained not reached with lorlatinib vs 9.1 months with crizotinib, HR 0.19 (95% CI 0.13–0.26) — an 81% reduction in the risk of progression or death. The probability of being alive and progression-free at 7 years was 55% (95% CI 46–63) with lorlatinib vs 3% (95% CI 1–8) with crizotinib — the longest PFS reported to date in advanced NSCLC. Intracranial benefit was maintained: time to intracranial progression not reached vs 16.4 months (12.7–21.9), HR 0.06 (95% CI 0.03–0.12), with no new intracranial progression events after 30 months. Longer follow-up showed very few additional PFS events; 44% of patients remained on lorlatinib at data cutoff, and patients event-free at 24 months had a 79% probability of 7-year PFS. Grade 3/4 AEs were higher with lorlatinib (77% vs 57%) but permanent discontinuation was low (5% vs 6%) with no new discontinuations after 26 months; dose reductions (34%) did not compromise efficacy. Overall survival data remain immature and are to be reported separately.

Mechanism / class

Lorlatinib (LORBRENA / Lorviqua) is a third-generation, brain-penetrant ALK/ROS1 tyrosine kinase inhibitor designed to cross the blood–brain barrier and to retain activity against a broad spectrum of ALK resistance mutations. FDA-approved for 1L ALK+ metastatic NSCLC (2021) on the basis of the CROWN primary analysis. Crizotinib is a first-generation ALK/ROS1/MET TKI.

Discussant takeaway

With median PFS still unreached at 7 years and 55% of patients progression-free, the discussion framed CROWN as setting a durability benchmark for oncogene-addicted NSCLC: an unprecedented PFS plateau, near-total CNS protection (intracranial HR 0.06, no new events after 30 months), and a long-term safety profile manageable by dose reduction without loss of efficacy. The principal caveat remains immature overall survival, to be reported separately.

Practice-changing?

Confirmatory rather than newly practice-changing. Lorlatinib is already an established first-line standard for ALK+ NSCLC; the 7-year update reinforces rather than changes practice. It entrenches lorlatinib as the preferred 1L option — an unprecedented plateau in PFS, durable CNS protection, and a manageable long-term safety profile — reinforcing existing NCCN/ESMO preferences without altering the standard of care.

Sources

  • ASCO Meeting Library (Abstract 8502): https://www.asco.org/abstracts-presentations
  • ASCO Meeting Library (related CROWN dose-modification abstract): https://www.asco.org/abstracts-presentations/ABSTRACT483582
  • Pfizer press release (7-year CROWN analysis): https://www.pfizer.com/news/press-release/press-release-detail/seven-year-analysis-pfizers-lorbrena-crown-trial-shows
  • OncLive: https://www.onclive.com/view/seven-years-strong-updated-crown-data-to-showcase-lorlatinib-s-durability-in-alk-nsclc-at-asco-2026
  • Managed Healthcare Executive: https://www.managedhealthcareexecutive.com/view/lorbrena-shows-persistent-pfs-benefit-at-7-years-in-alk-nsclc-asco-2026
  • Annals of Oncology (simultaneous publication): https://www.sciencedirect.com/science/article/pii/S0923753426008768
  • Lung Cancer Today: https://www.lungcancerstoday.com/post/crown-trial-lorlatinib-shows-unprecedented-and-highly-durable-benefit-in-advanced-alk-positive-nsclc
  • OncoDaily: https://oncodaily.com/not-to-miss/asco-511130