# Healthcare costs and health outcomes analysis of neoadjuvant Trastuzumab therapy for human epidermal growth factor receptor 2 (HER2) positive breast cancer

## TL;DR

This study compares the costs and health outcomes of using Trastuzumab as neoadjuvant, adjuvant, or combined therapy for HER2+ breast cancer, finding no major differences in effectiveness but higher costs for older patients.

## Contribution

The study provides a novel economic evaluation of neoadjuvant Trastuzumab therapy for HER2+ breast cancer in a real-world clinical setting.

## Key findings

- No significant difference in treatment cost, surgery cost, or DFS was found between adjuvant and neoadjuvant Trastuzumab groups.
- Older patients and those with Grade 3 tumors had significantly higher treatment costs.
- Adjuvant Trastuzumab was more cost-effective than neoadjuvant Trastuzumab, with ACERs of €18,828/QALY and €21,770/QALY, respectively.

## Abstract

Globally, the incidence of breast cancer continues to rise; however, mortality rates are declining due to the growing effectiveness of targeted therapies and treatments. Overexpression of human epidermal growth factor receptor 2 (HER2) is seen in ∼15% of breast cancers (termed HER2+). Trastuzumab is the standard HER2-targeted therapy for HER2+ breast cancers in the adjuvant setting, and is increasingly being used as a neoadjuvant chemotherapy treatment (NACT or NAC). However, as well as the clinical impact, using drugs in a different treatment setting (including neoadjuvant therapy) has a financial impact. Economic evaluation of novel chemotherapeutic strategies can assess both clinical utility and cost-effectiveness, thereby informing and guiding healthcare resource allocation decisions. Currently, the cost, clinical outcomes, and cost-effectiveness of single-agent neoadjuvant Trastuzumab remain underexplored. In this study, we evaluated the cost-effectiveness of Trastuzumab administered as neoadjuvant therapy, adjuvant therapy, or a combination of both regimens (NACT/ACT).

A 3-year retrospective observational comparative analysis was conducted to examine costs and health outcomes using clinicopathological data (treatment type, surgical procedure, breast cancer subtype) from a public hospital in Ireland. Overall, 192 non-metastatic, non-palliative HER2+ breast cancer patients (Luminal B HER2, and HER2+ [non-luminal]) were selected (151 adjuvant Trastuzumab treated, 28 neoadjuvant Trastuzumab treated, 13 NACT/ACT Trastuzumab treated). The analysis estimated the cost of treatment (chemotherapy regimen, surgery type) and health outcomes, which were evaluated by analysis of survival data, and by calculating quality-adjusted life years (QALYs) and average cost-effectiveness ratios (ACERs). Multivariate regression analysis, using survival regression model techniques, was performed to evaluate associations between treatment types and total costs-adjusted by age, stage, grade, and subtype. A Cox proportional hazard model estimated the effect of treatment alternatives for time to disease-free survival (DFS).

Multivariate analysis demonstrated no significant difference in treatment cost (p = 0.318), surgery cost (p = 0.951), or DFS (p = 0.236) between the adjuvant and neoadjuvant Trastuzumab treatment groups. A significantly higher treatment cost was observed in older patients (p = 0.011) and patients with Grade 3 tumours (p = 0.037). No significant difference in cost was found between the HER2 subtype groups (p = 0.129) or between disease stages (p = 0.71). No statistically significant difference in QALY was observed between adjuvant and neoadjuvant treatment groups (p = 0.296).

Overall, while adjuvant Trastuzumab remains the most cost-effective strategy for patients with HER2+ breast cancer, adopting a neoadjuvant Trastuzumab approach does not appear to pose a significant economic disadvantage. Notably, higher treatment costs were observed among older patients, a finding with important financial implications for healthcare systems. These results highlight the need for careful evaluation to inform forthcoming age-related cancer policy updates.

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•Treatment costs were significantly increased in older patients (p = 0.011).•No significant difference in quality-adjusted life years (QALYs) was observed between patients treated with adjuvant versus neoadjuvant Trastuzumab.•The average cost-effectiveness ratio (ACER) for adjuvant Trastuzumab was €18,828/QALY, compared with €21,770/QALY for neoadjuvant Trastuzumab.•No significant difference in DFS (3 years) was found between the neoadjuvant and adjuvant Trastuzumab groups.•Treatment costs did not differ significantly by type of surgery, breast cancer subtype, or the interaction between subtype and treatment.

Treatment costs were significantly increased in older patients (p = 0.011).

No significant difference in quality-adjusted life years (QALYs) was observed between patients treated with adjuvant versus neoadjuvant Trastuzumab.

The average cost-effectiveness ratio (ACER) for adjuvant Trastuzumab was €18,828/QALY, compared with €21,770/QALY for neoadjuvant Trastuzumab.

No significant difference in DFS (3 years) was found between the neoadjuvant and adjuvant Trastuzumab groups.

Treatment costs did not differ significantly by type of surgery, breast cancer subtype, or the interaction between subtype and treatment.