OBJECTIVES: Neratinib is an efficacious HER2-targeted agent for HER2+ ESBC, although its potential clinical benefits among the incident U.S. HR+ HER2+ high-risk ESBC patient population following use of T-DM1 or pertuzumab have not been quantified. Our objective was to estimate the long-term potential treatment benefits of neratinib in this target population.

METHODS: We developed a Markov model to quantify the prevention of local/regional and distant recurrences and deaths with the addition of neratinib (compared to no neratinib). We estimated population size from published sources, including population-based SEER and National Cancer Database electronic registries and clinical trials. High-risk was defined as HR+ patients who did not achieve a pathologic complete response (no pCR) with neoadjuvant therapy or were upstaged to stage IIB/III or higher following surgery for those only treated adjuvantly. Survival probabilities were extrapolated to a 10-year time horizon using parametric survival models derived from the ExteNET neratinib trial and clinical trials of T-DM1 (KATHERINE) and pertuzumab (APHINITY). The primary outcomes were recurrences (local/regional and distant) and breast cancer deaths prevented following neratinib treatment.

RESULTS: We calculated 10,654 (no pCR: 9,845; upstaged adjuvant: 809) incident high-risk patients who would potentially have neratinib treatment in the U.S. in 2022. Initial model results estimated neratinib use could potentially prevent 872 (829; 43, respectively) recurrences, including 784 (749; 35, respectively) distant recurrences and 632 (604; 28, respectively) breast cancer deaths over a 10-year period. Probabilistic sensitivity analyses indicated a range of 547 to 872 distant recurrences and 511 to 656 breast cancer deaths prevented.

CONCLUSIONS: Our model results suggest that among patients with high-risk HR+ HER2+ ESBC treated with extended adjuvant neratinib post-T-DM1 or -pertuzumab, a substantial number of recurrences and deaths might be prevented.