The Absolute Effect / Oncology Evidence / Evidence Index
CROWN
In untreated advanced ALK-positive NSCLC, does lorlatinib improve systemic and intracranial disease control over crizotinib?
Registry: NCT03052608 · Evidence reviewed 9 November 2026 · Aliases and follow-up publications consolidated.
Phase III randomized open-label; n=296.Primary-source evidence summaryStudy design, population and eligibility
Phase III randomized open-label; n=296.
Previously untreated advanced ALK-positive NSCLC.
Treatment and comparator
Intervention: Lorlatinib 100 mg daily.
Comparator: Crizotinib 250 mg twice daily.
Endpoints
PFS by BICR primary; long-term investigator PFS and intracranial outcomes.
Key efficacy and clinical outcomes
At ~5 y: median PFS NR vs 9.1 mo (HR 0.19); 5-y PFS 60% vs 8%; time to intracranial progression HR 0.06.
Source-reported outcome visualization
Values are reproduced from the cited report; bars are scaled within this figure. First-line ALK-positive advanced NSCLC
Median survival and hazard ratios are not fixed-time event risks; NNT is not inferred from them.
Toxicity and treatment burden
Hyperlipidaemia, oedema, weight gain, neuropathy and cognitive/mood effects.
Absolute effect and NNT/NNH
Crizotinib is an older comparator; not a head-to-head comparison with other modern ALK inhibitors.
NNT/NNH is not calculated unless a directly reported, comparable fixed-time risk difference supports it. Median survival and hazard ratios alone do not provide an NNT.
Critical interpretation and limitations
Crizotinib is an older comparator; not a head-to-head comparison with other modern ALK inhibitors.
This page is an evidence summary, not a substitute for multidisciplinary assessment or patient-specific decision-making.
Current-practice context
Review date: 9 November 2026. Primary publication and selected follow-up sources were reviewed. Full disease-specific guideline, regulatory-label and sequencing audit remains pending; verify current local recommendations and biomarker eligibility before clinical application.