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Lorlatinib outperforms crizotinib in ALK-positive advanced NSCLC

ESMO 2020
The phase 3 CROWN study showed superior efficacy of lorlatinib over crizotinib as a first-line treatment in patients with advanced ALK rearrangement-positive non-small cell lung cancer (NSCLC). Lorlatinib is a third generation ALK tyrosine kinase inhibitor that has shown overall and intracranial activity in advanced ALK rearrangement-positive NSCLC. In CROWN, 296 patients were randomised 1:1 to receive lorlatinib (100 mg once daily) or crizotinib (250 mg twice daily). Patients had stage III/IV ALK rearrangement-positive NSCLC and no prior systemic therapy for metastatic disease; asymptomatic treated or untreated brain metastases were permitted. The primary endpoint of CROWN was progression-free survival (PFS). At a preplanned interim analysis, PFS by BICR was significantly prolonged with lorlatinib versus crizotinib: not reached in the lorlatinib arm versus 9.3 months in the crizotinib arm (HR 0.28; P<0.001). 12-month P...

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