Assessment of the Cost-Effectiveness of HER2-Targeted Treatment Pathways in the Neoadjuvant Treatment of High-Risk HER2-Positive Early-Stage Breast Cancer

Introduction This study aims to assess differences in costs and benefits of treatment strategies for high-risk human epidermal growth factor receptor 2 positive (HER2+) early-stage breast cancer (ESBC). Methods We used a hybrid decision-tree/Markov model to simulate costs and outcomes across six health states: Invasive disease-free, non-metastatic recurrence, remission, first-line and second-line metastatic cancer, and death. We considered several strategies, defined by four attributes: (1) Neoadjuvant targeted therapy (infused pertuzumab and trastuzumab (PH) versus subcutaneous fixed-dose combination (FDC) of pertuzumab and trastuzumab versus trastuzumab alone (H)); (2) adjuvant targeted therapy if pathological complete response (pCR) is achieved (PH, FDC, or H); (3) adjuvant targeted therapy (T-DM1 or H) in the case of residual disease (RD); and (4) use of branded or biosimilar H. Transition probabilities were derived from relevant clinical trials. We included drug costs and costs associated with adverse events and administration. Health state utilities were obtained from clinical trials and the literature. Results Strategies not containing T-DM1 were dominated (worse outcomes and greater costs) by strategies containing T-DM1. Among strategies with pertuzumab continuation in the case of pCR and T-DM1 in the case of RD, use of FDC was dominant (equivalent outcomes and lower costs), relative to strategies using infused therapies, regardless of biosimilar versus branded trastuzumab. Adjuvant continuation of FDC was also cost-effective (better outcomes at reasonable cost increases) relative to strategies which discontinued pertuzumab following pCR. Conclusion Dual targeted therapy via FDC (with transition to T-DM1 in the case of RD) is a cost-effective treatment strategy in high-risk HER2+ ESBC.