Validity Assessment of Oncotype DX breast cancer assay economic analyses

Economic validity refers to the completeness, quality, and reliability of the analyses used to assess the economic implications of novel technologies. In 2003, Weinstein et al. outlined the criteria that should be considered when evaluating economic analysis.⁶ Four criteria have been established for systematically evaluating the quality and validity of economic evaluations, details of which are found in the appendix.

Six papers and one letter have been published in peer-reviewed journals on the potential economic implications of the Oncotype DX^® breast cancer assay in four countries (Table 1). Furthermore, six additional studies, representing five countries, have been presented as abstracts. In total, the implications of the Oncotype DX breast cancer assay have been evaluated in eight different countries.

Table 1. Summary of Health Economic Evidence

Economic Implications of Oncotype DX^® in the United States

In the first economic analysis of the Oncotype DX breast cancer assay in node-negative, ER-positive invasive breast cancer patients receiving tamoxifen, Hornberger et al. performed cost-utility analyses using a decision analytic model.⁷Using a Markov model, they forecasted overall survival, costs, and cost-effectiveness of using the Oncotype DX breast cancer assay results (Recurrence Score) in patients classified as having low or high risk of distant recurrence based on 2004 National Comprehensive Cancer Network^® (NCCN^®) clinical guidelines. Data from a large multicenter clinical trial (NSABP B-14) were analyzed to derive risk classifications based on guideline criteria and the Oncotype DX breast cancer assay. The effect of adjuvant chemotherapy (CT) on distant recurrence-free survival (DRFS) was based on published meta-analyses of CT trials. The analysis took a societal perspective, considering survival, quality of life, and relevant costs. Results showed fifty-three patients (8%) were classified as having low risk of distant recurrence by NCCN guidelines and the Oncotype DX breast cancer assay reclassified 15 of these patients (28%) to the intermediate or high risk groups. The remaining 615 patients (92%) were classified as having high risk of distant recurrence by NCCN guidelines and the Oncotype DX breast cancer assay reclassified 300 of these patients (49%) to low risk. Among a hypothetical cohort of 100 patients with node-negative, ER-positive early-stage invasive breast cancer (7.9% of whom are NCCN-classified as low risk for distant recurrence), use of the Oncotype DX breast cancer assay was expected to reclassify two patients from low risk to intermediate or high risk and 45 patients from high risk to low risk. Assuming patients with intermediate or high risk receive chemotherapy and patients at low risk do not, the Oncotype DX breast cancer assay was predicted to, on average, increase quality-adjusted survival by 8.6 years and reduce overall costs by $202 828 (Figure 3).

Figure 3. Cost effectiveness of the Oncotype DX breast cancer assay applied to cohort of 100 patients with node-negative, ER-positive early-stage invasive breast cancer

From Hornberger et al. Am J Manag Care 2005.⁷

The Oncotype DX breast cancer assay was cost saving in more than two-thirds of probabilistic simulations, with cost-effectiveness most influenced by the propensity to administer CT based on the Oncotype DX breast cancer assay results, and by the proportion of patients at low risk as defined by NCCN guidelines. Researchers concluded that the Oncotype DX breast cancer assay predicts recurrence risk in node-negative, ER-positive patients with early-stage invasive breast cancer more accurately than current guidelines.²⁰ If applied appropriately, the assay is predicted to increase quality-adjusted survival and save costs.

In a 2007 economic analysis of the cost-effectiveness of the Oncotype DX breast cancer assay, Lyman et al. assessed the efficacy of therapy guided by the Oncotype DX breast cancer assay results (Recurrence Score).⁸ Using data from NSABP studies B-14 and B-20, patients were classified as high (RS ≥31), intermediate (RS 18-30), or low (RS < 18) risk for distant recurrence at 10 years. Cost-effectiveness ratios were estimated for therapy guided by the Oncotype DX breast cancer assay compared with either tamoxifen alone or combined chemotherapy and tamoxifen. Therapy guided by the Oncotype DX breast cancer assay was associated with a gain in individual life expectancy of 2.2 years compared with tamoxifen alone, and with similar life expectancy to that seen with combined chemotherapy and tamoxifen. Therapy guided by the Oncotype DX breast cancer assay was estimated to provide a net cost savings of $2,256 compared with chemotherapy and tamoxifen with an incremental cost-effectiveness ratio of $1,944 per life year saved compared with tamoxifen alone (Figure 4).

Figure 4. Cost-effictiveness of Oncotype DX^® breast cancer assay

From Lyman et al. Cancer 2007.⁸

Researchers concluded that for patients with lymph node-negative, estrogen receptor-positive early-stage invasive breast cancer, treatment decisions based on therapy guided by the Oncotype DX breast cancer assay is associated with greater efficacy and acceptable cost-effectiveness ratios compared with tamoxifen alone. Compared with combined chemotherapy and tamoxifen, therapy guided by the Oncotype DX breast cancer assay is associated with similar efficacy and lower cost.

In 2010, Lo et al. at Loyola University Medical Center published the first prospective study on the decision impact of the Oncotype DX breast cancer assay.²¹ It inquired about reanalysis of the economic implications of the Oncotype DX breast cancer assay with their data. In response, Hornberger et al. applied the data reported by Lo et al. in the previously published decision analytic model and found a saving of more than $300 per patient tested.⁹

Hornberger et al. conducted a subsequent study in collaboration with Humana Inc., a large United States health insurance company, to examine the economic implications of adopting the Oncotype DX breast cancer assay within its health plan.¹⁵ Using published decision impact study of the Oncotype DX breast cancer assay and cost data obtained from retrospective claims analyses of 952 invasive breast cancer patients who were tested with the Oncotype DX breast cancer assay, the study found that, for Humana, the adoption of the Oncotype DX breast cancer assay was cost-saving (Figure 5).

Figure 5. Cost-effectiveness of Oncotype DX^® breast cancer assay adoption to Humana, Inc.

From Hornberger et al. Am J Manag Care 2011.¹⁵

To view the Hornberger et al. 2005 article please visit:http://www.ajmc.com/files/articlefiles/AJMC05MayHornbergr313to.pdf

To view the Lyman et al. 2007 article please visit: http://www3.interscience.wiley.com/cgi-bin/abstract/114124513/ABSTRACT

To view the Hornberger et al. 2011 article please visit: http://jop.ascopubs.org/content/7/3S/e38s.abstract?sid=7c228324-299f-44ff-bfb5-f15726ddfd19

National Comprehensive Cancer Network^® and NCCN^® are registered trademarks of NCCN, which does not endorse any product or therapy.Economic implications of the Oncotype DX^® breast cancer assay outside the United States

The economic implications of the Oncotype DX breast cancer assay have been evaluated in seven countries outside the United States (Table 2).

Table 2. Summary of health economic evidence outside the United States

References

6. Weinstein MC, O'Brien B, Hornberger J, et al. Principles of good practice for decision analytic modeling in health-care evaluation: report of the ISPOR Task Force on Good Research Practices--Modeling Studies. Value Health 2003;6:9-17.

7. Hornberger J, Cosler LE, Lyman GH. Economic analysis of targeting chemotherapy using a 21-gene RT-PCR assay in lymph-node-negative, estrogen-receptor-positive, early-stage breast cancer. Am J Manag Care 2005;11:313-24.

8. Lyman GH, Cosler LE, Kuderer NM, Hornberger J. Impact of a 21-gene RT-PCR assay on treatment decisions in early-stage breast cancer: an economic analysis based on prognostic and predictive validation studies. Cancer 2007;109:1011-8.

9. Hornberger J, Lyman GH, Chien R. Economic implications of 21-gene recurrence score assay: US multicenter experience. J Clin Oncol 2010;28:e382; author reply e3.

15. Hornberger J, Chien R, Krebs K, Hochheiser L. US insurance program’s experience with a multigene assay for early-stage breast cancer. Am J Manag Care 2011;17:e194-202.

20. Goldstein LJ, Gray R, Badve S, et al. Prognostic Utility of the 21-Gene Assay in Hormone Receptor-Positive Operable Breast Cancer Compared With Classical Clinicopathologic Features. J Clin Oncol 2008.

21. Lo SS, Mumby PB, Norton J, et al. Prospective multicenter study of the impact of the 21-gene recurrence score assay on medical oncologist and patient adjuvant breast cancer treatment selection. J Clin Oncol 2010;28:1671-6.