Cost­Effectiveness of Lorlatinib in First-Line Treatment of Adult Patients with Anaplastic Lymphoma Kinase (ALK)­Positive Non­Small­Cell Lung Cancer in Sweden.

BACKGROUND: We aimed to investigate the cost effectiveness of lorlatinib, a third-generation anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitor (TKI), used first-line in Sweden to treat patients with ALK-positive (ALK+) non-small cell lung cancer (NSCLC). In January 2022, the European Medicines Agency (EMA) extended its approval of lorlatinib to include adult patients with ALK+ NSCLC not previously treated with an ALK inhibitor. Extended first-line approval was based on results from CROWN, a phase III randomized trial that enlisted 296 patients randomized 1:1 to receive lorlatinib or crizotinib. Our analysis compared lorlatinib against the first-generation ALK-TKI crizotinib, and second-generation ALK TKIs alectinib and brigatinib. METHODS: A partitioned survival model with four health states [pre-progression, non-intracranial (non-central nervous system [CNS]) progression, CNS progression, and death] was constructed. The progressed disease state (which is typically modelled in cost-effectiveness analyses of oncology treatments) was explicitly separated into non-CNS and CNS progression as brain metastases, which are common in NSCLC, and can have a large impact on patient prognosis and health-related quality of life. Treatment effectiveness estimates in the lorlatinib and crizotinib arms of the model were derived from CROWN data, while indirect relative effectiveness estimates for alectinib and brigatinib were informed using network meta-analysis (NMA). Utility data were derived from the CROWN study in the base case, and cost-effectiveness results were compared when applying UK and Swedish value sets. Costs were obtained from Swedish national data. Deterministic and probabilistic sensitivity analyses were conducted to test model robustness. RESULTS: Fully incremental analysis identified crizotinib as the least costly and least effective treatment. Brigatinib was extendedly dominated by alectinib and, subsequently, alectinib was extendedly dominated by lorlatinib. Lorlatinib was associated with an incremental cost-effectiveness ratio (ICER) of Swedish Krona (SEK) 613,032 per quality-adjusted life-year (QALY) gained compared with crizotinib. Probabilistic results were generally consistent with deterministic results, and one-way sensitivity identified NMA HRs, alectinib and brigatinib treatment duration, and the CNS-progressed utility multiplier as key model drivers. CONCLUSIONS: The ICER of SEK613,032 for lorlatinib versus crizotinib falls below the typical willingness-to-pay threshold per QALY gained for high-severity diseases in Sweden (approximately SEK1,000,000). Furthermore, as brigatinib and alectinib were extendedly dominated in the incremental analysis, the results of our study indicate that lorlatinib may be considered a cost-effective treatment option for first-line patients with ALK+ NSCLC in Sweden when compared with crizotinib, alectinib, and brigatinib. Longer-term follow-up data for endpoints informing treatment effectiveness for all first-line treatments would help to reduce uncertainty in the findings.

Cost-effectiveness Analysis of Lorlatinib in Patients Previously Treated with Anaplastic Lymphoma Kinase Inhibitors for Non-small Cell Lung Cancer in Greece.

Background: Non-small cell lung cancer (NSCLC), which accounts for about 80%-85% of lungcancer cases, is a leading cause of cancer-related death worldwide. Lorlatinib is a potent third-generation anaplastic lymphoma kinase (ALK) inhibitor approved for the treatment of patients with advanced, ALK-positive NSCLC previously treated with at least one second-generation ALK tyrosine kinase inhibitor. Objective: The present study assessed the cost-effectiveness of lorlatinib vs pemetrexed with platinum combination of carboplatin or cisplatin (P-ChT) in Greece. Methods: A partitioned survival model with three health states, referring to pre-progression, progressed disease, and death, was locally adapted from a Greek payer perspective over a lifetime horizon. Clinical and safety data and utility values applied in the model were extracted from the literature. A matching-adjusted indirect comparison of lorlatinib and P-ChT was performed. Only direct medical costs (€) from 2020 were included in the analysis. Primary outcomes were patient life years (LYs), quality-adjusted life years (QALYs), total costs, and incremental cost-effectiveness ratios per QALY and LY gained. All future outcomes were discounted at 3.5% per annum. A probabilistic sensitivity analysis was conducted to account for model uncertainty. Results: The analysis showed that, over a lifetime horizon, the estimated total costs of lorlatinib and P-ChT were €81 754 and €12 343, respectively. Lorlatinib was more effective than P-ChT with 2.4 and 1.5 more LYs and QALYs gained, respectively. The generated incremental cost-effectiveness ratios of lorlatinib compared with P-ChT were €28 613 per LY gained and €46 102 per QALY gained. Probabilistic sensitivity analysis confirmed the deterministic results. Conclusion: The present analysis suggests that lorlatinib may be considered as a cost-effective option compared with P-ChT in Greece for the treatment of patients with advanced, ALK-positive NSCLC whose disease has progressed after at least one second-generation ALK tyrosine kinase inhibitor. In addition, this option addresses a significant unmet medical need.