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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 PFS rate in the lorlatinib arm was 78% versus 39% in the crizotinib arm. Lorlatinib favoured PFS in all pre-specified subgroups. Overall survival data are not yet mature. Objective response by BICR was improved by lorlatinib (76%) versus crizotinib (58%). The median duration of response was not reached in the lorlatinib arm versus 11.0 months in the crizotinib arm. In addition, median time to response was equal in both arms: 1.8 months. Intracranial response was superior for treatment with lorlatinib (see Table).

Table: Intracranial objective response in CROWN trail [1]

  1. Solomon B, et al. Lorlatinib vs crizotinib in the first-line treatment of patients (pts) with advanced ALK-positive non-small cell lung cancer (NSCLC): Results of the phase III CROWN study. ESMO 2020 Virtual Meeting, abstract LBA2.

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