Pfizer reported seven-year Phase 3 CROWN trial results showing LORBRENA reduced the risk of disease progression or death by 81% and delivered unprecedented long-term disease control in first-line ALK-positive NSCLC.
Written By: Mahathi Palivela, PharmD
Reviewed By: Pharmacally Editorial Team
Pfizer reported seven-year follow-up results from the Phase 3 CROWN trial (NCT03052608) showing sustained and clinically meaningful benefits with LORBRENA® (lorlatinib) in previously untreated patients with ALK-positive advanced or metastatic non-small cell lung cancer (NSCLC). The findings, presented at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting and published in Annals of Oncology, demonstrated durable disease control and long-term protection against brain metastases. The analysis represents the longest follow-up reported to date for a first-line ALK inhibitor, highlighting a major shift in treatment expectations for patients with ALK-positive NSCLC.
At seven years, 55% of patients receiving LORBRENA remained alive without disease progression compared with 3% of those treated with XALKORI® (crizotinib). Median progression-free survival (PFS) remained unreached for LORBRENA, translating to an 81% reduction in the risk of disease progression or death versus crizotinib.
Targeting a Challenging Lung Cancer Subtype
ALK-positive NSCLC accounts for approximately 3% to 5% of lung cancer cases and often affects younger patients. Brain metastases remain a major clinical concern, occurring in up to 40% of patients within two years of diagnosis.
LORBRENA is a third-generation ALK inhibitor developed to overcome resistance mutations and penetrate the blood-brain barrier, enabling durable control of both systemic and intracranial disease.
Durable Efficacy and Intracranial Protection
The randomized Phase 3 CROWN trial enrolled 296 patients with previously untreated ALK-positive advanced NSCLC. Participants received either LORBRENA (n=149) or crizotinib (n=147).
Long-term follow-up showed a hazard ratio for investigator-assessed PFS of 0.19, confirming a substantial and sustained treatment benefit. LORBRENA also reduced the risk of intracranial progression by 94% compared with crizotinib. No new intracranial progression events occurred after the first 30 months of treatment, and median time to intracranial progression was not reached.
Notably, 44% of patients remained on LORBRENA after seven years, compared with just 3% in the crizotinib arm.
Safety Remained Consistent Over Time
The safety profile aligned with previous reports, with no new safety signals identified. Common adverse events included edema, weight gain, peripheral neuropathy, cognitive effects, mood changes, hypercholesterolemia, and hypertriglyceridemia.
Grade 3/4 adverse events occurred in 77% of patients receiving LORBRENA versus 57% with crizotinib. However, treatment discontinuation due to treatment-related adverse events remained low at 5% and 6%, respectively.
Looking Ahead
Overall survival follow-up remains ongoing and represents a key secondary endpoint of the CROWN study. Future analyses will provide additional insight into the long-term survival impact of first-line lorlatinib treatment. With seven years of sustained disease control, durable intracranial protection, and nearly half of patients still receiving therapy, the latest CROWN data further reinforce LORBRENA’s position as the standard of care for first-line treatment of ALK-positive advanced NSCLC.
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About the Writer
Mahathi Palivela (LinkedIn) is pursuing PharmD and has a strong interest in Clinical Pharmacy and Patient safety. She is passionate about handling and analyzing patient data, and translating clinical insights into clear, meaningful summaries. She aims to apply this interest in Medical Writing and Pharmacovigilance, focusing on improving patient outcomes through careful data interpretation and communication.