Cost-effectiveness analysis of lorlatinib as first-line treatment for anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer in Italy.

[BACKGROUND] Lorlatinib is a third-generation anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitor (TKI) with high central nervous system penetration and activity against resistance mutations. Although its clinical efficacy as first-line treatment for ALK-positive advanced non-small cell lung cancer (NSCLC) has been demonstrated, its economic value within the Italian healthcare system remains to be fully established. This study evaluated the cost-effectiveness of lorlatinib compared with alectinib as first-line therapy in Italy.

[METHODS] A partitioned survival model with three health states (progression-free, progressed disease, and death) was developed from the Italian National Health Service and societal perspectives over a 30-year time horizon. Clinical efficacy inputs were derived from the CROWN trial and indirect treatment comparisons using network meta-analysis. Costs (2026 euros) included drug acquisition, subsequent treatments, healthcare resource use, adverse events, end-of-life care, and societal costs. Health outcomes were expressed as life-years (LYs) and quality-adjusted life-years (QALYs). Deterministic, probabilistic, and scenario analyses were conducted to assess uncertainty.

[RESULTS] In the base case, lorlatinib was dominant over alectinib, providing higher benefits (+2.01 LYs; +1.66 QALYs) at lower costs (-€19,210 per patient). This finding was robust across pricing scenarios. Probabilistic sensitivity analysis showed an almost 98,40% probability of cost-effectiveness at Italian willingness-to-pay thresholds.

[CONCLUSIONS] From both NHS and societal perspectives, lorlatinib represents a cost-saving and clinically superior first-line treatment option compared with alectinib for patients with ALK-positive advanced NSCLC in Italy.