OBJECTIVES : A recent clinical trial demonstrated that the use of neratinib after trastuzumab therapy significantly improves 24-month disease-free survival (93.9% vs 91.6%; HR 0.67, 95% CI 0.50 to 0.19) in women with early-stage human epidermal growth factor receptor 2 (HER2)-positive breast cancer. When neratinib was approved by the FDA in July 2017, controversies arose relating to its cost-effectiveness. We performed a cost-effectiveness analysis to evaluate the clinical and economic implications of adding neratinib to the clinical pathway for women with HER2-positive breast cancer following treatment with trastuzumab based on results of the pivotal neratinib trial NCT00878709.

METHODS : We created a 3-state Markov model to estimate the cost-effectiveness of up to 2 years of neratinib therapy following trastuzumab vs. a standard monitoring protocol only in cohorts of women with Stage I-III breast cancer. Two-year recurrence rates were based on ExteNET trial results. Rates of recurrence after 2 years and overall survival were drawn from the HERceptin Adjuvant (HERA) trial. We obtained direct medical expenditure inputs from the peer-reviewed literature. Costs and life-years were tracked over a lifetime horizon and used to estimate the incremental cost-effectiveness ratio. We took a payer perspective, considered costs in 2017 USD, and discounted all outcomes at 3% per year.

RESULTS : In the base case, the neratinib and standard care strategies resulted in 19.4 and 18.9 life years and $364,633 and $130,012 total cost. The cost per life year gained was $497,898. A one-way sensitivity analysis revealed the model was most sensitive to variations in the transition probability for progression to death.

CONCLUSIONS : We estimate that giving up to 2 years of neratinib following trastuzumab therapy is unlikely to be cost-effective relative to implied willingness-to-pay thresholds in the United States. As follow-up observational data becomes available, future analyses should reassess costs, effects, and cost-effectiveness associated with neratinib treatment.