Gene Expression Panels Less Cost-Effective in Real-World Settings

Gene expression profile tests may be less cost effective in realworld, clinical settings than previously thought, according to a study published Jan. 8 in the Journal of Clinical Oncology.

Oncotype DX (Genomic Health; Redwood City, Calif.) is the most commonly used, commercially available gene expression profile test and helps predict breast cancer recurrence. Under ideal, research protocols, the test was determined cost effective by current standards. However, this new study questions the test's cost effectiveness when used in community practice.

"As with all new technology, it's important to assess real-world implementation to ensure what we're offering patients is useful to them and doesn't add to the societal and patient cost-burden, which is already very high in cancer care," said the study's lead author, Young Chandler, Dr.P.H., from Georgetown University, in a statement.

Oncotype DX examines the activity of 21 genes in a patient's breast tumor tissue to predict the benefit of chemotherapy based on the risk of cancer recurrence. The test is intended for use in newly diagnosed patients with early-stage (stage I, II or IIIa), estrogen receptor-positive, HER2-negative breast cancer. Patients with test results indicating low-risk can consider skipping chemotherapy, while those with high-risk results are recommended to have chemotherapy. All major, U.S. insurance covers the test, the company says.

Unlike previous studies of Oncotype DX, which were conducted under ideal conditions—all patients received the test, the test's score dictated treatment decisions, and the test had prefect prediction of recurrence—this new research examines who is tested in real-world practice; how many patients at high risk of breast cancer recurrence do not act on treatment recommendations for chemotherapy; conversely, how many patients found to be at lower risk of recurrence chose to get chemotherapy anyway; and the impact of test accuracy on cost effectiveness.

The researchers created a model to compare 25-year incremental costs and quality-adjusted life-years (QALYs) based on community use of Oncotype DX from 2005 to 2012. Results were compared to usual care in the pretesting era (2000 to 2004).

From 2005 to 2012, testing rates among eligible patients in community practice were 24 percent and chemotherapy use rate was 30 percent. In community practice, treatment decisions sometimes ran contrary to test findings— 17 to 26 percent of patients with high-recurrence risk scores did not receive chemotherapy as guidelines recommend, and 8 percent of patients with low-risk scores still opted to receive chemotherapy.

The incremental cost-effectiveness ratio of breast cancer management using Oncotype DX testing as observed in community practice versus usual care without testing was $188,125 per QALY ($100,000 per QALY is the usual benchmark for cost effectiveness). The researchers found that under ideal conditions, including perfect test accuracy, the cost-effectiveness ratio was $39,496 per QALY, which is more similar to earlier estimates.

However, cost-effectiveness increased under different scenarios, including lower test costs, higher test accuracy, greater adherence to test-suggested treatment, and consideration of the benefits of testing on quality of life.

• If Oncotype DX costs declined from $3,416 (the current Medicare reimbursement rate, to $2,657, then the incremental cost-effectiveness ratio of community practice versus usual care decreased to $71,250 per QALY.

• Adherence to test-concordant treatment lowered the cost-effectiveness ratio to $85,490 per QALY.

• Factoring in the affects of worry or reassurance as a result of information on recurrence risk, the incremental cost-effectiveness ratio for Oncotype DX testing was $58,431 per QALY.

In response to the study, Genomic Health provided a statement to HemOnc Today, which noted limitations of the study's model, including the assumption that Kaiser Permanente patient and testing data was representative of all of community practice. The company added, "Cost-effectiveness analyses are very complex and highly sensitive to the assumptions underlying the economic model. "To truly understand the economics of diagnostic testing, it is important to look for consistency across multiple economic studies."

Takeaway: New data suggests that gene expression profile testing (Onco Dx, specifically) may be less cost-effective in actual community practice than under the ideal circumstances of research protocols.