Tumour profiling tests to guide adjuvant chemotherapy decisions in early breast cancer: a systematic review and economic analysis

Abstract

Background Breast cancer and its treatment can have an impact on health-related quality of life and survival. Tumour profiling tests aim to identify whether or not women need chemotherapy owing to their risk of relapse. Objectives To conduct a systematic review of the effectiveness and cost-effectiveness of the tumour profiling tests oncotype DX® (Genomic Health, Inc., Redwood City, CA, USA), MammaPrint® (Agendia, Inc., Amsterdam, the Netherlands), Prosigna® (NanoString Technologies, Inc., Seattle, WA, USA), EndoPredict® (Myriad Genetics Ltd, London, UK) and immunohistochemistry 4 (IHC4). To develop a health economic model to assess the cost-effectiveness of these tests compared with clinical tools to guide the use of adjuvant chemotherapy in early-stage breast cancer from the perspective of the NHS and Personal Social Services. Design A systematic review and health economic analysis were conducted. Review methods The systematic review was partially an update of a 2013 review. Nine databases were searched in February 2017. The review included studies assessing clinical effectiveness in people with oestrogen receptor-positive, human epidermal growth factor receptor 2-negative, stage I or II cancer with zero to three positive lymph nodes. The economic analysis included a review of existing analyses and the development of a de novo model. Results A total of 153 studies were identified. Only one completed randomised controlled trial (RCT) using a tumour profiling test in clinical practice was identified: Microarray In Node-negative Disease may Avoid ChemoTherapy (MINDACT) for MammaPrint. Other studies suggest that all the tests can provide information on the risk of relapse; however, results were more varied in lymph node-positive (LN+) patients than in lymph node-negative (LN0) patients. There is limited and varying evidence that oncotype DX and MammaPrint can predict benefit from chemotherapy. The net change in the percentage of patients with a chemotherapy recommendation or decision pre/post test ranged from an increase of 1% to a decrease of 23% among UK studies and a decrease of 0% to 64% across European studies. The health economic analysis suggests that the incremental cost-effectiveness ratios for the tests versus current practice are broadly favourable for the following scenarios: (1) oncotype DX, for the LN0 subgroup with a Nottingham Prognostic Index (NPI) of > 3.4 and the one to three positive lymph nodes (LN1–3) subgroup (if a predictive benefit is assumed); (2) IHC4 plus clinical factors (IHC4+C), for all patient subgroups; (3) Prosigna, for the LN0 subgroup with a NPI of > 3.4 and the LN1–3 subgroup; (4) EndoPredict Clinical, for the LN1–3 subgroup only; and (5) MammaPrint, for no subgroups. Limitations There was only one completed RCT using a tumour profiling test in clinical practice. Except for oncotype DX in the LN0 group with a NPI score of > 3.4 (clinical intermediate risk), evidence surrounding pre- and post-test chemotherapy probabilities is subject to considerable uncertainty. There is uncertainty regarding whether or not oncotype DX and MammaPrint are predictive of chemotherapy benefit. The MammaPrint analysis uses a different data source to the other four tests. The Translational substudy of the Arimidex, Tamoxifen, Alone or in Combination (TransATAC) study (used in the economic modelling) has a number of limitations. Conclusions The review suggests that all the tests can provide prognostic information on the risk of relapse; results were more varied in LN+ patients than in LN0 patients. There is limited and varying evidence that oncotype DX and MammaPrint are predictive of chemotherapy benefit. Health economic analyses indicate that some tests may have a favourable cost-effectiveness profile for certain patient subgroups; all estimates are subject to uncertainty. More evidence is needed on the prediction of chemotherapy benefit, long-term impacts and changes in UK pre-/post-chemotherapy decisions. Study registration This study is registered as PROSPERO CRD42017059561. Funding The National Institute for Health Research Health Technology Assessment programme.

Recommendations from the European Commission Initiative on Breast Cancer for multigene testing to guide the use of adjuvant chemotherapy in patients with early breast cancer, hormone receptor positive, HER-2 negative

“…Unfortunately, we were unable to deduce the details of the ASCO evidence rating approach and also the criteria and judgments that were used to determine the strength of the recommendations. Unlike us, ASCO and NICE made recommendations on the 12-MS and the PAM50-RORS to guide treatment decisions, 55 , 62 mainly because they did not exclude studies based on prognostic results only.…”

Cost-effectiveness analysis of genomic profiling in early breast cancer in Colombia

“…A costeffectiveness study conducted by the UK National Institute for Excellence in Health and Care found that neither ODX nor MMP are cost effective from the perspective of the UK health system. 39 No predictive role of the bene t of chemotherapy was considered for ODX or MMP. Notably, at the time of performing this analysis, the results of the TAILORx trial were unknown, which demonstrated the ability of ODX to establish the bene t of adjuvant chemotherapy and not only its ability to establish prognosis.…”

The Potential Use of Tumour-Based Prognostic and Predictive Tools in Older Women with Primary Breast Cancer: A Narrative Review

“…The Prosigna assay (based on the PAM50 signature) measures 58 genes (50 cancer-related genes and eight controls) and classifies a patient’s tumour into a subtype based on the signature (luminal A, luminal B, HER-2 enriched or basal-like) [ 46 ]. The test is designed for postmenopausal women with early, ER-positive, HER2-negative breast cancer with up to three positive lymph nodes, receiving 5 years of hormonal therapy [ 14 ].…”