Comparative Efficacy and Safety of Lorlatinib and Alectinib for ALK-Rearrangement Positive Advanced Non-Small Cell Lung Cancer in Asian and Non-Asian Patients: A Systematic Review and Network Meta-Analysis

SIMPLE SUMMARY: The treatment of anaplastic lymphoma kinase (ALK) rearrangement-positive (ALK-p) advanced non-small cell lung cancer (NSCLC) remains a challenge. We compared the safety and efficacy of lorlatinib and alectinib in patients with ALK-p ALK-inhibitor‒naïve advanced NSCLC (in overall participants and in the Asian and non-Asian subgroups). The results showed that in the overall participant group, the efficacy of lorlatinib and alectinib was not significantly different in terms of progression-free survival (PFS) and overall survival (OS). Although in the Asian subgroup, PFS was not significantly different upon treatment with lorlatinib or alectinib, in the non-Asian subgroup, PFS was significantly better in response to lorlatinib than with alectinib. Grade 3 or higher adverse events in the overall participant group were significantly more frequent with lorlatinib than with alectinib. These results will provide valuable information that would enable the improvement of treatment strategies for ALK-p ALK-inhibitor‒naïve advanced NSCLC. ABSTRACT: To date, there have been no head-to-head randomized controlled trials (RCTs) comparing the safety and efficacy of lorlatinib and alectinib in anaplastic lymphoma kinase (ALK) rearrangement-positive (ALK-p) ALK-inhibitor‒naïve advanced non-small cell lung cancer (NSCLC). We performed a network meta-analysis comparing six treatment arms (lorlatinib, brigatinib, alectinib, ceritinib, crizotinib, and platinum-based chemotherapy) in overall participants and in Asian and non-Asian subgroups. Primary endpoints were progression-free survival (PFS), overall survival (OS), and grade 3 or higher adverse events (G3-AEs). There were no significant differences between lorlatinib and alectinib in overall participants for both PFS (hazard ratio [HR], 0.742; 95% credible interval [CrI], 0.466–1.180) and OS (HR, 1.180; 95% CrI, 0.590–2.354). In the Asian subgroup, there were no significant differences in PFS between lorlatinib and alectinib (HR, 1.423; 95% CrI, 0.748–2.708); however, in the non-Asian subgroup, PFS was significantly better with lorlatinib than with alectinib (HR, 0.388; 95% CrI, 0.195–0.769). The incidence of G3-AEs in overall participants was significantly higher with lorlatinib than with alectinib (risk ratio, 1.918; 95% CrI, 1.486–2.475). These results provide valuable information regarding the safety and efficacy of lorlatinib in ALK-p ALK-inhibitor‒naïve advanced NSCLC. Larger head-to-head RCTs are needed to validate the study results.