US population-level model of clinical impact of lorlatinib treatment on ALK+ metastatic non-small cell lung cancer outcomes

Aim: Lorlatinib and alectinib are next-generation anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKIs) approved for the treatment of ALK-positive (ALK+) advanced/metastatic non-small cell lung cancer (NSCLC) after demonstrating superior efficacy over crizotinib (first-generation ALK TKI) in the CROWN and ALEX trials, respectively. This analysis estimated the US population-level clinical impact of first-line (1L) lorlatinib versus alectinib treatment for ALK+ advanced/metastatic NSCLC. Materials & methods: We developed a decision-analytic model comparing lorlatinib versus alectinib use in 1L. We used a three-state partitioned survival model (pre-progression, post-progression and death) and tracked incidence of brain metastases (BMs). Lorlatinib-eligible population estimates were derived from published literature and market forecasts; treatment effectiveness for lorlatinib was derived from CROWN; alectinib comparative effectiveness was informed using a match-adjusted indirect comparison (CROWN vs ALEX). We assumed lorlatinib uptake of 38% in the base case; selected scenarios included different survival extrapolations, assuming 100% lorlatinib uptake and applying risk of BM post-discontinuation. Results: We estimated that 3096 patients in the US would be eligible for lorlatinib. Compared with 1L alectinib use only, our model projected that 1L lorlatinib treatment results in 1620–5170 and 1590–4880 more life-years and quality-adjusted life-years, respectively, over a 20-year time horizon across scenarios. Per-patient incidence of BM ranged from 0.14–0.18 and 0.21–0.40 for lorlatinib and alectinib, respectively, resulting in 68–256 fewer BMs. Separately, for every 5–15 patients treated with 1L lorlatinib instead of 1L alectinib, one BM would be avoided. Conclusion: This analysis projected that 1L lorlatinib treatment in the US could result in more LYs and quality-adjusted life-years and fewer BMs versus 1L alectinib in ALK+ advanced/metastatic NSCLC.

Lorlatinib and alectinib are newer drugs approved for the first-line (1L) treatment of anaplastic lymphoma kinase-positive (ALK+) advanced/metastatic non-small cell lung cancer (NSCLC). Although both lorlatinib and alectinib have demonstrated better efficacy over crizotinib, an older drug in the same class, no head-to-head trials have been conducted to compare lorlatinib and alectinib to each other. While modeling studies have been conducted to compare these two drugs, the population-level clinical impact of adopting lorlatinib over alectinib has not been quantified.

This study estimated the US population-level clinical impact in terms of life years (LYs), quality-adjusted life years (QALYs) and incidence of brain metastases (BMs), of selecting 1L lorlatinib versus 1L alectinib in ALK+ advanced/metastatic NSCLC populations. QALYs are estimated by weighting time in each health state (progression-free, progressed disease) by the quality of life weight for each health state. Lorlatinib was associated with gains in LYs, QALYs, and reductions in BMs, compared with alectinib. Overall, lorlatinib availability was projected to yield meaningful population-level benefits under different modeled assumptions.

The findings provide quantitative evidence supporting lorlatinib as a 1L treatment for ALK+ advanced/metastatic NSCLC. With consistent gains in LYs and QALYs and a reduction in BMs, the results can help inform reimbursement decisions, clinical guideline updates and formulary considerations favoring broader access to lorlatinib.