Lorlatinib Significantly Improves Survival vs Crizotinib in Patients With ALK-Positive Advanced NSCLC Regardless of Brain Metastases

Treatment with lorlatinib was associated with improved progression-free survival (PFS) vs crizotinib among patients with anaplastic lymphoma kinase (ALK)-positive non-small-cell lung cancer (NSCLC), with or without brain metastases according to findings from the phase 3 CROWN study.

“Brain metastases develop in more than half of patients with ALK-positive [NSCLC]; these are associated with poor prognosis, high symptom burden, and decreased quality of life,” explained Benjamin Solomon, PhD, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia, and colleagues.

The phase 3 CROWN study enrolled 296 patients with advanced ALK-positive NSCLC who had not received prior systemic treatment. Patients were randomly assigned 1:1 to receive 100mg first-line lorlatinib once a day (n = 149) or twice daily 250mg crizotinib (n = 147), and were stratified based on the presence of brain metastases and ethnicity. The primary outcomes was PFS. This post hoc analysis reported data on efficacy outcomes in patients with and without brain metastases at baseline, with occurrence and management of central nervous system adverse events derived from present data.

At the data cutoff date of March 20, 2020, blinded independent central review showed longer progression-free surival in patients with and without brain metastases at baseline with lorlatinib (12-month PFS rate: 78% in both groups) vs crizotinib (12-month PFS rates: 22% and 45% with and without brain metastases, respectively). Patients with and without brain metastases treated with lorlatinib reported lower 12-month cumulative incidences of central nervous system progression (7% and 1% respectively) when compared to those treated with crizotinib (72% and 18%, respectively).

Central nervous system adverse events occurred in 35% of patients treated with lorlatinib. Most adverse events were grade 1, with no clinically meaningful difference in quality of life. At the time of analysis, 33% of central nervous system adverse events were resolved with no intervention required, and 17% were resolved by modifying lorlatinib dosage. There was no notable change to progression-free survival due to this dose modification.

Study authors concluded, “Our data support lorlatinib as first-line treatment in patients with advanced ALK-positive NSCLC with/without brain metastases.”

Source:                                        

Solomon BJ, Bauer TM, Ou SI, et al. Post hoc analysis of lorlatinib intracranial efficacy and safety in patients with ALK-positive advanced non-small-cell lung cancer from the phase III CROWN study. J Clin Oncol. Published online: May 23, 2022. doi:10.1200/JCO.21.02278