Lorbrena Approved for First-Line Treatment of ALK-Positive Metastatic NSCLC

Lorbrena is a third generation ALK tyrosine kinase inhibitor.

The Food and Drug Administration (FDA) has expanded the approval of Lorbrena® (lorlatinib) to include first-line treatment of patients with anaplastic lymphoma kinase (ALK)-positive metastatic non-small cell lung cancer (NSCLC). Lorbrena is now indicated for adults with metastatic NSCLC whose tumors are ALK-positive as detected by an FDA-approved test.

The expanded approval was based on data from the phase 3 CROWN trial (ClinicalTrials.gov: NCT03052608), which included 296 patients with previously untreated advanced ALK-positive NSCLC. Patients were randomly assigned to receive lorlatinib 100mg once daily (n=149) or crizotinib 250mg twice daily (n=147); the primary end point of the study was progression free survival (PFS).

Results showed a significant improvement in PFS for the lorlatinib arm over the crizotinib arm (hazard ratio 0.28; 95% CI, 0.19-0.41; P <.0001). The overall response rate was 76% (95% CI, 68-83) for the lorlatinib group and 58% (95% CI, 49-66) for the crizotinib group. Seventy percent of lorlatinib-treated patients responded to treatment for 12 months or longer compared with 27% of crizotinib-treated patients.

Among patients with measurable intracranial lesions, the intracranial tumor response rate was 82% (95% CI, 57-96) in the lorlatinib arm and 23% (95% CI, 5-54) in the crizotinib arm. The intracranial duration of response was 12 months or longer in 79% of patients in the lorlatinib group and 0% in the crizotinib group.

Commenting on the approval, Andy Schmeltz, Global President, Pfizer Oncology, said: “Lorbrena has been a transformative medicine for people with ALK-positive advanced NSCLC, and this FDA approval in the first-line setting means that we can now extend hope to even more people.”

Lorbrena is supplied as 25mg and 100mg strength tablets.


1.      U.S. FDA expands approval of Pfizer’s Lorbrena® as first-line treatment for ALK-positive metastatic lung cancer. [press release]. New York, US: Pfizer; March 3, 2021.

2.      Lorbrena [prescribing information]. New York, NY; Pfizer. March 2021.