Authors' objectives: The objective was to investigate the prognostic accuracy, clinical effectiveness, and cost effectiveness of Prosigna in patients diagnosed with breast cancer. In Norway, the group considered as potentially eligible for the test is patients with breast cancer who had their tumor removed, are node-negative and where the tumor is classified as hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-).

Authors' results and conclusions: Prognostic accuracy: There is convincing evidence of a correlation between the observed risk of recurrence and the risk stratification score generated by the Prosigna test. For patients classified as low risk, the ten-year risk of recurrence is around 4%. For the intermediate risk group, the risk is around 10%, and for the high-risk group around 21%. We also expressed the performance of the test in terms of prognostic sensitivity and specificity. When we merged the intermediate risk group with the low risk group (intermediate test constitutes a “negative” test), we estimated the test’s sensitivity to 52%, and its specificity to 77%. If the intermediate group was merged with the high-risk group (intermediate risk constitutes a “positive” test), the sensitivity and specificity were estimated to be 83% and 42%, respectively. The estimates presented above reflect the test’s performance when used as a standalone tool. In practice, it can be anticipated that the test will be used as a supplement to the current risk stratification approaches. Clinical effectiveness: We did not identify comparative studies where patients were allocated to risk stratification with or without the Prosigna and followed over time. Without such comparative studies, it is difficult to estimate the clinical utility of Prosigna, i.e. Prosigna’s impact on the use of chemotherapy and patient outcomes such as disease-free survival and side effects from chemotherapy. Studies exploring the prognostic value of adding Prosigna to other prognostic variables in multivariate regression models suggest that Prosigna adds prognostic information that may be useful when deciding about further use of chemotherapy. However, these data are sparse, and it remains unclear to what extent Prosigna will contribute to fewer recurrences or a reduction in the needless use of chemotherapy than current practice. Health economics: The incremental cost-effectiveness ratio (ICER) based on the revised economic model for HR+/ HER2-, node negative patients, is calculated to NOK 897,923 per QALY gain in our base-case analysis. The estimate is based on questionable assumptions and is highly sensitive to changes in the chemotherapy use parameter. We estimated the total added costs of implementing Prosigna for this group in Norway, to about NOK .5 million in year five. The calculated incremental cost-effectiveness ratio (ICER) based on the revised economic model for the subgroup of “Luminal B like pT1c-pT2 pN0”-patients (38% of the “all node negative”-population) would be NOK 98,188 per QALY gain. Implementing Prosigna for this subgroup in Norway, would lead to a total cost saving of NOK 9.9 million in year five. There is probably a statistical association between Prosigna's risk prediction and the observed risk of distant recurrence after breast cancer. However, it is uncertain to what extent Prosigna contributes prognostic information that translates into better clinical results in terms of lower recurrence rates and reduced chemotherapy use Conclusion: Conclusions about the cost-effectiveness of Prosigna cannot be made as we do not have reliable data on chemotherapy use and clinical outcomes for patients who have or have not undergone Prosigna testing.

Authors' methods: Prognostic accuracy and clinical effectiveness: To validate the submitted evidence we extracted data from the key publications and critically appraised the risk of bias in the findings. Health economics: We assessed cost‐effectiveness estimates of Prosigna compared with current practice for HR+/ HER2-, node negative patients, provided by the submitter, and similarly for a defined subgroup of patients at higher risk of recurrence (“Luminal B like pT1c-pT2 pN0”). The estimates were based on a hybrid model with a decision tree combined with a Markov model. Cost-effectiveness estimates for Prosigna versus current practice were modelled over a 50-year time horizon, for patients aged 58. We performed separate analyses using the submitted model, adjusting some of the input variables based on revised assumptions. Also, we performed alternative scenario analyses for differences in chemotherapy use with and without use of the Prosigna test, based on various other data sources.

Project Status: Completed

Year Published: 2019

URL for published report: https://www.fhi.no/en/publ/2019/Prosigna_Gene_Signature_to_Assess_Expected_Benefit_from_Chemotherapy_in_Breast_Cancer/

English language abstract: An English language summary is available

Publication Type: Full HTA

Country: Norway

Organisation Name: Norwegian Institute of Public Health

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