OBJECTIVES ALK+ NSCLC is an aggressive subtype of lung cancer with high rates of Central Nervous System (CNS) metastasis, with 15-35% of patients presenting brain metastases at diagnosis, leading to a major clinical burden and a high economic impact on national healthcare systems (NHS). Crizotinib, a first-generation tyrosine kinase inhibitor (TKI), currently used in the Portuguese setting as first-line (1L) treatment, has shown limited CNS efficacy – 70% of patients experience CNS disease progression during treatment with crizotinib. Recently, the Portuguese healthcare authority (INFARMED) recognized that both alectinib and brigatinib, two next-generation TKIs, have higher clinical benefit than crizotinib in the 1L setting. The aim of this study is to assess which of these regimens is the most sustainable choice in a resource constrained NHS, such as the Portuguese setting.

METHODS An analytic decision model, based on the results of the ALTA-1L study and on a matching-adjusted indirect comparison, was developed to compare the clinical and economic outcomes of replacing the 1L ALK+ NSCLC standard of care in Portugal - crizotinib and alectinib - with brigatinib.

RESULTS For an estimated population of 236 newly diagnosed ALK+ NSCLC patients in 2021, brigatinib is expected to avoid disease progression and CNS invasion in an additional number of 58 and 47 patients, respectively, versus crizotinib in a 2-year time horizon, while allowing for the extension of 1L treatment by 16 months. Brigatinib and alectinib provide similar clinical results, however, brigatinib results in a 10% annual cost reduction versus the latter.

CONCLUSIONS : Brigatinib represents a sustainable option for ALK+ NSCLC 1L treatment in Portugal. Treatment with brigatinib showed superior clinical efficacy compared to crizotinib and similar efficacy to alectinib, while allowing for greater daily dosage convenience than alectinib (one versus eight pills) and economic savings for the Portuguese NHS.