Retrospective cohort study of comparative real-world effectiveness of first-line targeted therapies in ALK-positive non-small cell lung cancer

A retrospective cohort study using Optim’s de-identified Clinformatics Data Mart Database (2016-2024) compared real-world effectiveness of first-line (1L) anaplastic lymphoma kinase tyrosine kinase inhibitors (ALK TKIs) in adult patients with ALK-positive non-small cell lung cancer. Outcomes were time-to-next treatment or death (TTNTD) and overall survival (OS). Propensity scores were constructed for pairwise comparisons and applied using overlap weighting (OW) as the primary specification and inverse probability of treatment weighting (IPTW) as alternative specification. The study included 940 patients initiating IL therapy (449 crizotinib, 417 alectinib, 36 lorlatinib, 30 brigatinib, 8 ceritinib). Alectinib had the longest reached TTNTD (33.5 months; 95% CI 24.6-46.3) and OS (46.5; 39.0-NR) in unadjusted analyses. In OW analysis, alectinib was associated with significantly longer TTNTD (HR 0.50; 95% CI 0.41-0.61) and OS (0.58; 0.47-0.71) versus crizotinib. Comparison of alectinib versus lorlatinib statistically insignificantly favored lorlatinib. The authors conclude that alectinib demonstrated a clear real-world survival advantage over crizotinib; where lorlatinib may have benefit over alectinib.