A matching-adjusted indirect comparison of first-line lorlatinib and alectinib for the treatment of ALK-rearranged advanced non-small cell lung cancer

Background: In the lack of head-to-head trials comparing lorlatinib and alectinib, we aimed to assess the effectiveness of lorlatinib versus alectinib as first-line treatment for advanced ALK-rearranged non-small cell lung cancer (NSCLC), with a focus on Asian population. Methods: In this comparative effectiveness study, the data on the lorlatinib group were obtained from the CROWN trial. Following the CROWN trial's inclusion criteria, real-world adult patients with advanced ALK-rearranged NSCLC who received first-line alectinib between January 1, 2017 and February 27, 2024, from the Samsung Medical Center were included in the alectinib group. Using matching-adjusted indirect comparison (MAIC), hazard ratios (HRs) and their 95 % confidence intervals (CIs) for overall survival (OS), progression-free survival (PFS), and intracranial (IC)-PFS were evaluated based on Cox proportional hazard models. Results: A total of 223 patients were included in the alectinib group with effective sample size of 90.2 and 178.1 after MAIC against the overall (multiracial) and Asian populations in the CROWN trial, respectively. Compared to the multiracial population, OS (HR, 1.52; 95 % CI, 0.77–2.99) and PFS (HR, 1.03; 95 % CI, 0.67–1.59) were not significantly different between the alectinib and lorlatinib groups. Consistently, PFS and OS of the alectinib group were not significantly different from those of the Asian lorlatinib group (HR, 1.31; 95 % CI, 0.80–2.14). IC-PFS was not significantly different between the two drugs, regardless of race. Conclusions: First-line lorlatinib showed comparable efficacy to alectinib especially in Asian population. Further long-term and race-specific data are needed to guide more precise treatment decisions.