Lorlatinib Continues to Outperform Crizotinib in 36-Month CROWN Follow-Up

By: Celeste L. Dixon
Posted: Thursday, March 30, 2023

The 36-month follow-up data from the randomized phase III CROWN trial confirmed the efficacy of lorlatinib over crizotinib in patients with treatment-naive, ALK-positive non–small cell lung cancer (NSCLC), supporting lorlatinib’s use in this population, irrespective of the presence of brain metastases. Additionally, no new safety signals were detected, reported Enriqueta Felip, MD, PhD, of Vall d’Hebron Institute of Oncology, Barcelona, and colleagues in their work presented during the Journal of the Advanced Practitioner in Oncology conference JADPRO Live (Abstract JL1041E).

In fact, of 112 patients without baseline brain metastases taking lorlatinib—a third-generation ALK inhibitor designed to cross the blood-brain barrier—just 1 had evidence of intercranial disease progression. Previously, the team had shown that lorlatinib improved progression-free survival (the study’s primary endpoint) and demonstrated intracranial activity in these patients. The cohort included 296 patients with previously untreated advanced ALK-positive NSCLC who were randomly assigned on a 1:1 basis to oral lorlatinib (n = 149) or crizotinib (n = 147), stratified by the presence of central nervous system metastases and ethnicity.

The updated data were based on a median duration of follow-up for progression-free survival of 36.7 months for lorlatinib and 29.3 months for crizotinib. The median progression-free survival by blinded independent central review was not reached for lorlatinib and 9.3 months for crizotinib (hazard ratio = 0.27), with similar results for progression-free survival by investigator.

For patients with brain metastases at baseline (n = 37 for lorlatinib; n = 39 for crizotinib), the hazard ratio for intercranial time to disease progression for lorlatinib versus crizotinib was 0.10 and for patients without brain metastases (n = 112 and n = 108, respectively), the hazard ratio was 0.02, Dr. Felip and co-investigators reported. Additionally, the secondary endpoints of objective response, intercranial objective response, duration of response, and intercranial duration of response were all improved with lorlatinib versus crizotinib, they wrote. The study is ongoing.

Disclosure: The study authors’ disclosure information can be found at eventscribe.net.

Journal of the Advanced Practitioner in Oncology

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