Cost-Effectiveness Analysis of the Oncotype DX Breast Recurrence Score® Test in Node-Negative Early Breast Cancer

Abstract

Background: The 21-gene assay (the Oncotype DX Breast Recurrence Score^® test) is a validated multigene assay which produces the Recurrence Score^® result (RS) to inform decisions on the use of adjuvant chemotherapy in human epidermal growth factor receptor 2-negative (HER2-), hormone receptor positive (HR+) early invasive breast cancer. A model-based economic evaluation estimated the cost-effectiveness of the 21-gene assay against the use of clinical risk tools alone based on the latest evidence from prospective studies.

Methods: The proportion of patients assigned to chemotherapy conditional on their RS result was obtained from retrospective data from the Clalit registry. The probability of distant recurrence with endocrine and chemo-endocrine therapy conditional on RS result was obtained from TAILORx and NSABP B-20 trials. The cost-effectiveness of the 21-gene assay compared to using clinical risk tools alone was estimated in terms of cost per quality-adjusted life-year (QALY) over a lifetime horizon.

Results: The 21-gene assay was more effective (0.17 more quality-adjusted life years) at a lower cost (-£519) over a lifetime compared to clinical risk alone. The model results were sensitive to assumptions around the magnitude of benefit of chemotherapy in the high RS result subgroup. Other assumptions underpinning the model, such as the proportion of patients assigned to chemotherapy in the low and mid-range RS result subgroups and long-term distant recurrence probabilities, had a smaller impact on the results.

Conclusion: The analysis showed that the cost-effectiveness of the 21-gene assay is sensitive to assumptions for chemotherapy sparing for patients with RS 0-25 whose outcomes with endocrine therapy are no worse compared to chemotherapy-assigned patients, and a chemotherapy benefit in the RS 26-100 group. Future studies need to incorporate a wider set of tumour profiling tests other than the 21-gene assay to allow a direct comparison of their cost-effectiveness.

Keywords: 21-gene assay; breast cancer; chemotherapy; cost-effectiveness; multigene assay; the Oncotype DX test.

Figure 1

Diagram of the decision-tree part of the model. The square node represents the decision whether to use tumour profiling tests, and which MGA to use. The circle nodes are chance nodes representing the distribution of genomic risk and chemotherapy assignment. The triangle nodes are the terminal nodes for the decision tree and the point at which patients enter the Markov portion of the model.

Figure 2

Markov model diagram representing the four health states.

Figure 3

Proportion of patients assigned to chemo-endocrine therapy after using the 21-gene assay and clinical risk alone.

Figure 4

Tornado diagram representing the change in the net monetary benefit (NMB) for the 21-gene assay associated with a change of individual parameter values. Plausible parameter ranges were obtained from published 95% confidence intervals or constructed from reported standard errors. In the absence of reported ranges or standard errors, arbitrary ranges were used based on ±20% deviation from the expected value. White bars represent an increase in the parameter value and black bars represent a decrease in the parameter value.

Figure 5

Scatter diagram representing incremental costs and QALYs generated using the probabilistic sensitivity analysis. The solid line represents the NICE cost-effectiveness threshold of £20,000 per QALY.

Figure 6

Cost-effectiveness acceptability curve generated using the probabilistic sensitivity analysis, which represents the proportion of PSA observations below different thresholds of cost-effectiveness (£ per QALY). The solid line corresponds to the probability of cost-effectiveness of the 21-gene assay compared to clinical risk alone and the dashed line represents the probability of cost-effectiveness of the comparator.