Authors' objectives: The objective of the STA was to appraise the evidence addressing the following questions: (Q1) Can Oncotype DX predict chemotherapy benefit? (Q2) Does Oncotype DX provide prognostic information? (Q3) What is the distribution of RS in populations of breast cancer patients? (Q4) Can Oncotype DX reduce chemotherapy use? We also appraised the cost-effectiveness and budget impact analyses provided by the submitter.

Authors' results and conclusions: Clinical effectiveness: The submitter identified four RCTs that investigated whether Oncotype DX can predict chemotherapy benefit in patients with ER+ HER- early-stage breast cancer. Two of the RCTs investigated patients with node negative disease and two investigated node positive disease (1-3 positive lymph nodes). Additional RCTs were not identified in our separate literature search. For patients with node negative disease (regardless of menopausal status) and for postmenopausal patients with node positive disease, there was convincing evidence that: Patients with low or intermediate RS (0-25) have similar risk of recurrence regardless of whether they are treated with endocrine therapy plus chemotherapy or endocrine therapy alone (have no chemotherapy benefit). However, a small chemotherapy benefit was observed for node negative women below 50 years and a RS of 16-25. Patients with high RS (>25) treated with endocrine therapy plus chemotherapy have lower risk of recurrence than those treated with endocrine therapy alone (have chemotherapy benefit). RCTs and non-randomized studies also demonstrated that Oncotype DX provides prognostic information. Distributions of RS suggested that approximately 75-90% of the patients with node negative and node positive disease have low or intermediate RS (0-25) and can omit chemotherapy. Decision-impact studies demonstrated that Oncotype DX reduced chemotherapy assignment by 16-27% for node negative patients and by 50-73% for node positive patients. The studies also illustrated that treatment decisions were not based entirely on the RS. Health economics: The base case cost-effectiveness analysis indicated that Oncotype DX was dominant compared to assessment of traditional clinical parameters (no gene-profiling test) for both node negative and postmenopausal node positive patients (i.e., provided greater QALY gains at a lower cost). One way sensitivity analyses identified the primary sources of uncertainty in the model. These were the hazard ratio for the high RS group for node negative patients, and the hazard ratio for the low and intermediate RS group for postmenopausal node positive patients. Probabilistic sensitivity analyses showed that, with a willingness-to-pay threshold of 250,000 NOK per QALY, the Oncotype DX test had a probability of 99% and 100 % of being cost-effective (compared to no gene profiling test) for node negative and postmenopausal node positive patients respectively. Absolute shortfall of QALYs was calculated to be 1.83 QALYs. Budget impact analyses showed net costs of implementing Oncotype DX (compared to no gene-profiling test) for node negative patients, and net savings for postmenopausal node positive patients, each of the five years following implementation. The budget impact analysis for the entire population showed net costs each of the five years. The analyses are associated with uncertainty.

Authors' methods: Clinical effectiveness: We performed a separate literature search to evaluate whether all randomized controlled trials (RCTs) addressing question Q1 were found and included by the submitter. We extracted data from the RCTs and critically appraised the risk of bias. Our confidence in the results was assessed using the GRADE approach. We also extracted data from RCTs and non-randomized studies to validate the submitted evidence for question Q2, Q3, and Q4. Health economics: The health economic model provided by the submitter combined a decision tree and a Markov model to compare the Oncotype DX test strategy to assessment of traditional clinical parameters (no gene-profiling test). Patients were categorised as having low, intermediate or high RS, and in each RS group, patients received or did not receive chemotherapy. These groups were connected to a Markov model that predicted lifetime QALYs and costs, considering the risk of distant recurrence. The submitter also performed sensitivity analyses and budget impact analyses.

Project Status: Completed

Year Published: 2023

URL for published report: https://www.fhi.no/en/publ/2023/Oncotype-DX-breast-cancer-recurrence-score-test/

English language abstract: An English language summary is available

Publication Type: Not Assigned

Country: Norway

Organisation Name: Norwegian Institute of Public Health

Contact Address: P.O. Box 222 Skoyen, N-0123, Oslo