Neoadjuvant treatment strategies for HER2-positive breast cancer: cost-effectiveness and quality of life outcomes.

Abstract

Achieving a pathologic complete response (pCR) with neoadjuvant therapy for HER2-positive breast cancer is associated with less recurrence and improved clinical outcomes compared to having residual cancer at surgery. However, recent data have demonstrated favorable outcomes for patients with residual HER2-positive cancer who received adjuvant trastuzumab emtansine (TDM-1). Therefore, we sought to determine the optimal chemotherapy/anti-HER2 treatment strategy. We created a decision-analytic model for patients with stage II-III HER2-positive cancer that incorporated utilities based on toxicity and recurrence. We separately modeled hormone receptor-negative (HR-) and positive (HR+) disease and calculated quality-adjusted life years (QALYs) and costs through 5years. Simulated patients received one of the following neoadjuvant treatments: three 'intensive' regimens (TCHP: docetaxel, carboplatin, trastuzumab, pertuzumab; THP + AC: taxol, trastuzumab, pertuzumab then doxorubicin and cyclophosphamide; THP: taxol, trastuzumab, pertuzumab) and two 'de-escalated' regimens (TH: taxol, trastuzumab; TDM-1) followed by adjuvant treatment based on pathologic response. Among 'intensive' neoadjuvant strategies, treatment with THP was more effective and less costly than TCHP or THP + AC. When 'de-escalated' strategies were included, TH became the most cost-effective. For HR-negative cancer, TH had 0.003 fewer quality-adjusted life years (QALYs) than THP but was less costly by $55,831, resulting in an incremental cost-effectiveness ratio of over $18M/QALY for THP, well above any threshold. For HR-positive cancer, neoadjuvant TH dominated the THP strategy. An adaptive-treatment strategy beginning with neoadjuvant THP or TH followed by tailoring post-operative therapy reduces treatment costs, and spares toxicity compared to more intensive chemotherapy regimens for women with HER2-positive breast cancer.