OBJECTIVES: Second generation ALK-inhibitors have shown improvement in brain disease control compared with Crizotinib in patients with metastatic ALK+ NSCLC. However, Crizotinib is the only treatment covered by the Brazilian private health care system (BHCS) so far. The objective of this study was to evaluate the cost-effectiveness of first-line Brigatinib in patients with ALK+ NSCLC and brain metastases at diagnosis, in comparison with Crizotinib and Alectinib, according to BHCS perspective. METHODS: Cost-effectiveness analysis was performed using a Markov model and a 10-year time horizon. Data from three pivotal trials (PROFILE 1014, ALEX and ALTA-1L) informed the efficacy inputs. Resource consumption and utilities were obtained from the literature. Drug costs were taken from the Medicine Market Regulation Chamber (CMED), as published in August 2020, in Brazilian Reais (R$). The incremental cost-effectiveness ratio (ICER) for each comparison was calculated from the health insurers’ perspective. A 5% discount rate was applied to costs and outcomes. Deterministic and probabilistic sensitivity analyses were performed to assess the robustness of results. RESULTS: This model identified that Brigatinib used as first-line treatment is dominant, in comparison to Crizotinib (ICER: - R$135,547) and Alectinib (ICER: -R$85,046). Sensitivity analyses showed that these results are robust and depend, mainly, on the probability of death for patients treated with Brigatinib. During the sensitive analysis, assuming a probability of death of 0.24 at the end of first year, the upper limit of the confidence interval, results an ICER of -R$600,000. CONCLUSIONS: First line treatment with Brigatinib in patients with ALK+ NSCLC and brain metastases at diagnosis can be cost-effective, according to the BHCS perspective. This can be seen as an opportunity to enhance local health care sustainability, with the potential to improve the prognosis of ALK+ NSCLC even in patients with brain metastases at diagnosis.

This study was funded by Takeda Farmacêutica Brasil.