OBJECTIVES: Lorlatinib is a potent 3^rd generation anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitor (TKI) approved for the first line treatment of patients with ALK positive advanced non-small cell lung cancer (ALK+ aNSCLC). The present study evaluated the cost-effectiveness of lorlatinib compared to 1^st generation ALK TKI crizotinib, and 2^nd generation TKIs alectinib and brigatinib, which are currently used in clinical practice in Greece.

METHODS: A partitioned survival model with four health states (pre-progression, non-CNS, CNS progression and death) was adapted from a Greek payer perspective over a lifetime horizon. Clinical, safety data, and utility values were extracted from relevant clinical trials and a network meta-analysis comparing the effectiveness of lorlatinib and the other therapeutic alternatives was performed. Direct medical costs (in €) obtained from official sources (for 2023) were included in the analysis. Model outcomes were patients’ life years (LYs), quality-adjusted life years (QALYs), total costs and incremental cost-effectiveness ratios (ICERs) per QALY and LY gained.

RESULTS: Total lifetime cost per patient with lorlatinib, alectinib, crizotinib and brigatinib was estimated to be €188,205, €183,343, €75,028, and €145,454 respectively. In terms of health outcomes, lorlatinib was associated with 1.13, 3.33 and 2.58 increment in LYs compared with alectinib, crizotinib, and brigatinib respectively. Furthermore, lorlatinib appeared to yield more QALYs gained versus alectinib, crizotinib and brigatinib (5.47 vs 4.37, 3.12 and 3.84 respectively). Lorlatinib incremental analysis resulted in ICERs of €4,315 per LY gained and €4,422 per QALY gained compared to alectinib, €34,032 per LY gained and €48,256 per QALY gained versus crizotinib and €16,587 per LY gained and €26,271 per QALY gained compared to brigatinib.

CONCLUSIONS: Lorlatinib provides substantial clinical benefit versus current therapeutic alternatives and appears to be a cost–effective treatment option compared to 1^st and 2^nd generation TKIs for previously untreated patients with ALK+ aNCSLC in Greece.