OBJECTIVES : To evaluate the cost-effectiveness of tucatinib in human epidermal growth factor receptor 2 (HER2)-positive breast cancer (BC) patients with brain metastases (BMs) and the subgroup of active BMs from the United States (US) payer perspective.

METHODS : A three-state Markov model was developed to compare the cost-effectiveness of tucatinib, trastuzumab and capecitabine (TTC) with placebo, trastuzumab and capecitabine (PTC) in HER2-positive BC patients with BMs;subgroup analysis of active BMs was also performed.Pseudo-individual patient data were generated from digitized Kaplan-Meier curves.Costs were derived from official databases and the literature.Health state utility values were consistent with published literature and adjusted by adverse events.Lifetime costs,quality-adjusted life years (QALYs),incremental cost-effectiveness ratio (ICER) and incremental net health benefit (INHB) were estimated.The willingness-to-pay (WTP) threshold was $200,000/QALY.The robustness of the model was tested by sensitivity analysis and scenario analyses were also performed.

RESULTS : In patients with BMs,the PTC and TTC strategies cost $87,905.23 and $503,637.21,yielding 0.68 and 1.68 QALYs,respectively.While in the subgroup of active BMs,the two strategies cost $81,968.50 and $451,699.62 and the QALYs were 0.61 and 1.75,respectively.The ICERs yielded by TTC were $418,007.01/QALY and $324,465.03/QALY, and INHBs were -1.08 QALYs and -0.71 QALY, compared with PTC in these two groups,respectively.The results were most sensitive to the cost of tucatinib.Probabilistic sensitivity analysis suggested that the probability of TTC being cost-effective was low at the current WTP threshold in the patients with BMs and the subgroup of active BMs.

CONCLUSIONS : The additional using tucatinib (TTC) is unlikely to be cost-effective in HER2-positive BC patients with BMs from the US payer perspective,but shows a better economics in patients with active BMs.Therefore, selecting favorable population would be a good way to optimize the cost-effectiveness of tucatinib.To meet the economical demands of public health,it may be a preferable option to reduce the price of tucatinib or offer appropriate drug assistance policies.