OBJECTIVES : To construct a cost-effectiveness model reflective of the evolving treatment paradigm in HER2+ metastatic breast cancer (mBC) and assess the cost effectiveness of trastuzumab deruxtecan (T-DXd), a HER2-targeting antibody–drug conjugate, versus tucatinib+trastuzumab+capecitabine in patients with HER2+ mBC who are resistant or refractory to [ado-] trastuzumab emtansine, from a US third-party payer’s perspective.

METHODS : A partitioned-survival model was created to compare the cost-effectiveness of T-DXd versus tucatinib+trastuzumab+capecitabine over a 20-year time horizon. Efficacy and safety data for T-DXd and tucatinib+trastuzumab+capecitabine were derived from the single-arm DESTINY-BREAST01 and placebo-controlled HER2CLIMB phase 2 trials, respectively. A matching-adjusted indirect comparison (MAIC) was conducted to derive the relative effect of T-DXd on progression-free survival (PFS). Overall survival (OS) gain for T-DXd was estimated using an assumed surrogacy relationship between mean PFS and OS gain. Health state utility values, resource use and costs were based on published sources.

RESULTS : T-DXd dominated tucatinib+trastuzumab+capecitabine with an incremental gain of 0.49 quality-adjusted life-years (QALYs) and a negative incremental cost (decrement) of $83,784, when assuming a 1:1.5 incremental PFS:OS surrogacy relationship. T-DXd remained dominant when the estimated PFS gain without OS gain was assumed in scenario analyses. Results were robust in one-way sensitivity and scenario analyses, with all scenarios tested resulting in a positive incremental QALY gain and negative incremental cost

LIMITATIONS: This analysis is subject to inherent uncertainty due to the use of single-arm trial data and the immaturity of currently available OS data for T-DXd. Differences in key baseline characteristics between the trial populations resulted in low effective sample size and wide confidence interval in the MAIC.

CONCLUSIONS : T-DXd may be an economically dominant treatment strategy when compared to tucatinib+trastuzumab+capecitabine as a 3L option in patients with HER2+ mBC from a US third-party payer perspective. Further data from ongoing trials will help reduce uncertainty in this finding.