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.