A cost-consequence model of using the 21-gene assay to identify patients with early-stage node-positive breast cancer who benefit from adjuvant chemotherapy in the Netherlands

Abstract

Background

Patients with early-stage hormone receptor positive, human epidermal growth factor receptor-2 (HER2) negative invasive breast cancer with 1–3 positive lymph nodes (N1) often undergo surgical excisions followed by adjuvant chemotherapy (ACT). Many patients have no benefit from ACT and receive unnecessary, costly treatment often associated with short- and long-term adverse events (AEs). Gene expression profiling (GEP) assays, such as the 21-gene assay (i.e. the Oncotype DX assay), can identify patients at higher risk for recurrence who may benefit from ACT. However, the budgetary consequence of using the Oncotype DX assay versus no GEP testing in the Netherlands is unknown. Our study therefore assessed it using a cost-consequence model.

Methods

A validated model was used to create the N1 model. The model compared the costs and consequences of using the Oncotype DX assay versus no GEP testing and MammaPrint, and subsequent ACT use with corresponding costs for chemotherapy, treatment of AEs, productivity losses, GEP testing, and treatment of recurrences, according to the Oncotype DX results. The model time horizon was 5 years.

Results

Costs for the total population amounted to €8.0 million (M), €16.2 M, and €9.5 M, and cost per patient amounted to €13,540, €27,455, and €16,154 for using the Oncotype DX assay, no GEP testing, and MammaPrint, respectively. Total cost savings of using the Oncotype DX assay amounted to €8.2 M versus no GEP testing and €1.5 M versus MammaPrint. Using the Oncotype DX assay would result in fewer patients receiving ACT and thus fewer AEs, sick days, and hospitalizations, leading to overall cost savings compared with no GEP testing and MammaPrint.

Conclusions

Implementing Oncotype DX testing in this population can prevent unnecessary overtreatment, reducing clinical and economic burden on the patient and Dutch healthcare system.

PLAIN LANGUAGE SUMMARY

Early-stage invasive breast cancer patients often undergo surgery followed by adjuvant chemotherapy. However, many of these patients have no benefit from adjuvant chemotherapy and thus receive unnecessary and costly treatment often associated with side-effects. Patients who may benefit from adjuvant chemotherapy can be identified by analyzing the genomic profile of the patients’ tumors using a molecular diagnostic test called the 21-gene assay (also known as Oncotype DX assay). However, the budgetary consequences of using Oncotype DX for this purpose in the Netherlands are currently unknown and, therefore, assessed using a health-economic model. The model compared the costs and consequences of using the Oncotype DX assay versus no molecular diagnostic testing and an alternative molecular diagnostic test called MammaPrint. The three diagnostic testing strategies resulted in different costs in terms of several different costing categories and were compared with one another. The total costs were lowest for the diagnostic strategy using the Oncotype DX assay, as it would result in fewer patients receiving adjuvant chemotherapy compared with no molecular diagnostic testing and MammaPrint. Implementing the Oncotype DX assay as a molecular diagnostic test can identify the right patient who benefits from chemotherapy (prevent over- and undertreatment) and lead to cost-savings, reducing the clinical and economic burden on the patient and Dutch healthcare system.

Keywords:

• 21-gene
• gene expression profiling
• early stage
• hormone receptor
• human epidermal growth factor receptor 2
• breast cancer
• lymph node positive
• adjuvant chemotherapy
• cost-consequence analysis

JEL CLASSIFICATION CODES:

• A11
• A1
• A
• C21
• C2
• C
• C51
• C5

Transparency

Declaration of funding

This work was supported by Exact Sciences.

Disclosure statement

MS, JS, and TI were employed by OPEN Health during the conduct of the study and report consulting fees from Exact Sciences. OPEN Health is a consultancy firm that was contracted by Exact Sciences to conduct the study and help write the manuscript. FJ was contracted as advisor and reports personal fees from Exact Sciences. PD, TJ, and PM were employed by Exact Sciences during the conduct of the study and report no conflicts of interest.

Author contributions

Concept and design: MS, FJ, JS, PM; Analysis and interpretation of the data: MS, JS, TI, TJ, PM; Drafting the paper or revising it critically for intellectual content: MS, FJ, JS, TI, PD, TJ, PM; Gave final approval for the version to be published: MS, FJ, JS, TI, PD, TJ, PM; Agree to be accountable for all aspects of the work: MS, FJ, JS, TI, PD, TJ, PM.

Acknowledgements

The authors thank the medical colleagues from Exact Sciences for critically reviewing the manuscript. Furthermore, the authors thank Monique Pijls from Exact Sciences and the funding organization for the support and making this research possible.

Data availability statement

The input data supporting this cost-consequence model are from previously reported publications and reports, which have been cited. No datasets were generated or analyzed during the current study.

Reviewer disclosures

All the peer reviewers on this manuscript have received an honorarium from JME for their review work. One of the reviewers on this manuscript has disclosed that they are a consultant for Agendia and Myriad Genetics.

Notes

* Oncotype DX assay is short for the 21-gene Oncotype DX Breast Recurrence Score assay.