First-line lorlatinib versus crizotinib in ALK-positive non-small cell lung cancer: Asian subgroup analysis of CROWN

Abstract

Background: Lorlatinib, a 3rd-generation ALK inhibitor, significantly prolonged progression-free survival (PFS) vs crizotinib in the CROWN trial in patients with untreated ALK-positive non-small cell lung cancer (NSCLC). We report data from the Asian subgroup of CROWN. Methods: In this ongoing phase III trial (NCT03052608), untreated patients (n = 296) with ALK-positive advanced NSCLC were randomised to lorlatinib or crizotinib, stratified by presence of brain metastases and ethnicity (Asian/non-Asian). The primary endpoint was PFS by blinded independent central review. Primary and key secondary endpoints were analysed in the Asian subgroup (unstratified analyses). Results: In the Asian subgroup, 120 patients were randomised (59 to lorlatinib, 61 to crizotinib [1 not treated]): 48 in Japan, 21 South Korea, 20 mainland China, 16 Taiwan, 8 Singapore and 7 Hong Kong. Baseline characteristics (median age: 61 and 55 years; female: 46% and 61% for lorlatinib and crizotinib, respectively) were similar to the overall population except for a slightly greater gender imbalance between treatments. Lorlatinib prolonged PFS and increased overall and intracranial response vs crizotinib (Table). The most common any-grade adverse events (AEs) with lorlatinib were hypertriglyceridaemia (68%), hypercholesterolaemia (68%), oedema (44%) and weight increased (42%), and with crizotinib were nausea (58%), diarrhoea (58%), vomiting (45%), vision disorder (43%) and constipation (42%). Grade 3/4 AEs were reported by 78% (lorlatinib) vs 60% (crizotinib). Fewer patients had AEs leading to permanent treatment discontinuation in the lorlatinib arm (6.8%) than the crizotinib arm (11.7%). Conclusions: In the Asian subgroup, a consistent and clinically meaningful improvement in PFS was observed for lorlatinib vs crizotinib. The efficacy and safety of lorlatinib vs crizotinib in the Asian subgroup of CROWN was consistent with the overall population.