Real-World Clinical and Economic Consequences of Next-Generation Anaplastic Lymphoma Kinase-Positive (ALK +) Tyrosine Kinase Inhibitors (TKIs) in Patients with TKI-Naïve ALK + Metastatic Non-Small Cell Lung Cancer in the United States.

introductionThis study evaluated the real-world utilization, effectiveness, occurrence of adverse events (AEs), and healthcare costs in patients treated with next-generation anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKI), alectinib, brigatinib, and lorlatinib, among ALK TKI-naïve patients with ALK rearrangement-positive metastatic non-small cell lung cancer (ALK + mNSCLC) in the US.

methodsThis retrospective, observational cohort study used Veradigm electronic health records linked with Komodo closed claims. Eligible patients were adults with ALK + mNSCLC diagnosis who received their first ALK TKI (alectinib, brigatinib, or lorlatinib) between 5/22/2020 (US FDA approval of first-line brigatinib) and 12/31/2024. Descriptive analyses included baseline patient demographics, clinical characteristics, occurrence of AEs, and treatment patterns. Unweighted Cox proportional hazards models and propensity score-weighted Cox proportional hazards models were conducted to compare real-world treatment effectiveness [real-world time to treatment discontinuation (rwTTD), real-world time to next treatment (rwTTNT), real-world progression-free survival (rwPFS), real-world overall survival (rwOS)], and all-cause healthcare utilization and costs across ALK TKIs.

resultsA total of 481 patients (alectinib: 391; brigatinib: 32; lorlatinib: 58) were included. Mean age ranged from 58.5 to 63.7 years across the three treatment groups; more than half of the patients were female (less than half male), White, or covered by commercial insurance. In the unweighted and weighted analyses, there were no statistically significant differences in rwTTD, rwTTNT, rwPFS, or rwOS between treatment groups. Mean weighted all-cause healthcare costs per-patient-per-month during the index TKI treatment duration were not significantly different across cohorts (alectinib: US$20,873; brigatinib: $25,693; lorlatinib: $24,984).

conclusionThis study found no statistically significant differences in real-world clinical effectiveness and total all-cause healthcare costs between alectinib, brigatinib, or lorlatinib for ALK TKI-naïve patients with ALK + mNSCLC. Future studies with larger sample sizes and longer follow-up time are needed to confirm these findings.