Lorlatinib is used in selected patients with ALK-positive non-small cell lung cancer. Regulatory indications differ in wording between jurisdictions.
United States
Current FDA labeling indicates LORBRENA for adults with metastatic NSCLC whose tumors are ALK-positive, as detected by an FDA-approved test.
The current U.S. indication therefore includes treatment of metastatic ALK-positive NSCLC without limiting the indication to patients who previously received another ALK inhibitor.
European Union
The EMA’s current product information describes Lorviqua as monotherapy for adults with ALK-positive advanced NSCLC who have not previously been treated with an ALK inhibitor, and for adults whose disease has progressed after specified prior ALK TKI regimens.
ALK testing
ALK status is central to treatment selection. The FDA requires an FDA-approved test for the ALK-positive designation in the U.S.
A diagnosis of NSCLC alone does not establish that lorlatinib is indicated.
Brain metastases
Lorlatinib has important intracranial activity because the medicine reaches the central nervous system. In the five-year CROWN analysis, intracranial progression was substantially delayed compared with crizotinib.
First-line treatment
The phase III CROWN study compared lorlatinib with crizotinib in 296 previously untreated patients with advanced ALK-positive NSCLC. At five years, median progression-free survival had not been reached with lorlatinib, while it was 9.1 months with crizotinib.
A 2026 seven-year update reported that 55% of patients in the lorlatinib arm remained alive without disease progression at seven years, although these are trial-level results and do not predict an individual’s outcome.
Previously treated disease
Lorlatinib was originally approved in the United States for patients with metastatic ALK-positive NSCLC whose disease had progressed on prior ALK inhibitor therapy. Pfizer’s initial approval announcement described its role in patients whose disease had progressed following previous treatment.
Approved versus investigational use
Clinical trials may investigate lorlatinib in settings that are not included in a particular country’s authorized indication. Research activity should not be interpreted as regulatory approval.