992P Updated analyses from the CROWN study of first-line lorlatinib vs crizotinib in Asian patients with ALK-positive non-small cell lung cancer (NSCLC)

Abstract

Lorlatinib improved progression-free survival (PFS) and demonstrated intracranial (IC) activity in patients with untreated advanced ALK+ non-small cell lung cancer (NSCLC) in the phase III CROWN study (NCT03052608) of lorlatinib vs crizotinib. Here, we report updated results in the Asian subgroup from this study after 36 months of follow-up. Patients were randomized 1:1 to receive lorlatinib 100 mg once daily or crizotinib 250 mg twice daily, stratified by presence of brain metastases (yes/no) and ethnicity (Asian/non-Asian). The primary endpoint was PFS by based on blinded independent central review (BICR). Key secondary endpoints included objective response rate (ORR), intracranial ORR (IC ORR), IC time to progression (IC TTP), and safety. Endpoints were analyzed using unstratified analyses in the Asian subgroup. In the Asian subgroup, 120 patients were randomized to lorlatinib (n=59) or crizotinib (n=61) arm. At data cutoff (Sep 20, 2021), median PFS by BICR was not reached with lorlatinib and 11.1 months with crizotinib (HR 0.40; 95% CI, 0.230-0.710; Table). Both ORR and IC ORR were clinically improved with lorlatinib vs crizotinib. The HR of IC TTP with lorlatinib vs crizotinib was 0.03 (95% CI, 0.004-0.200). All-cause grade 3/4 treatment-emergent adverse events (TEAEs) and TEAEs leading to treatment discontinuation were reported in 79.7% and 8.5% of patients with lorlatinib and 61.7% and 13.3% of patients with crizotinib, respectively. No new safety signals emerged.Table: 992PEfficacy in CROWN Asian subgroupaEndpointLorlatinib (n=59)Crizotinib (n=61)PFS, median (95% CI), monthsNR (33.1-NR)11.1 (9.2-14.8)HR (95% CI)0.40 (0.230-0.710)ORR (95% CI), %78.0 (65.3-87.7)57.4 (44.1-70.0)IC TTP (95% CI), monthsNR (NR-NR)16.6 (11.0-NR)HR (95% CI)0.03 (0.004-0.200)Patients with brain metastases at baselineLorlatinib (n=11)Crizotinib (n=15)IC ORR (95% CI), %72.7 (39.0-94.0)20.0 (4.3-48.1)HR, hazard ratio; IC, intracranial; NR, not reached; ORR, objective response rate; PFS, progression-free survival; TTP, time to progression. aBy blinded independent central review unless stated otherwise. Open table in a new tab HR, hazard ratio; IC, intracranial; NR, not reached; ORR, objective response rate; PFS, progression-free survival; TTP, time to progression. aBy blinded independent central review unless stated otherwise. Efficacy and safety results in the Asian subgroup were consistent with those in the overall population in the CROWN study. Our data support the use of lorlatinib as a first-line treatment option in Asian patients with ALK+ NSCLC.