Disclaimer
This information collection is a core HTA, i.e. an extensive analysis of one or more health technologies using all nine domains of the HTA Core Model. The core HTA is intended to be used as an information base for local (e.g. national or regional) HTAs.

Prognostic tests for breast cancer recurrence (uPA/PAI-1 [FEMTELLE], MammaPrint, Oncotype DX )

UPA/PAI-1 (FEMTELLE), MammaPrint, Oncotype DX compared to Standard of care in selecting treatment for Breast cancer recurrence in females

(See detailed scope below)

HTA Core Model Application for Diagnostic Technologies (1.1)
Core HTA
Published
Tom Jefferson (age.na.s, Italy), Nicola Vicari (age.na.s, Italy), Heike Raatz (SNHTA, Switzerland)
Sarah Baggaley, NICE (Health problem and current use); Antonio Migliore, Agenas (Description and technical characteristics); Iris Pasternack, THL-FINOHTA (Safety); Mirjana Huic, AAZ (Clinical effectiveness), Isaura Vieira, INFARMED (Costs and economic evaluation); Dario Sacchini, A.Gemelli (Ethical analysis); Jennifer Butt, NICE (Organisational aspects); Marco Marchetti, A.Gemelli (Social and Legal aspects)
Agenzia nationale per i servizi sanitari regionali (age.na.s), Italy
A. Gemelli (Italy), AAZ (Croatia), Agenas (Italy), AHTAPol (Poland), AVALIA-t (Spain), INFARMED (Portugal), IPH-RS (Slovenia), NICE (United Kingdom), Regione Veneto (Italy), SNHTA (Switzerland), THL (Finland), UMIT (Austria)
13.6.2011 14.00.00
31.1.2013 18.05.00
Jefferson T, Vicari N, Raatz H [eds.]. Prognostic tests for breast cancer recurrence (uPA/PAI-1 [FEMTELLE], MammaPrint, Oncotype DX ) [Core HTA], Agenzia nationale per i servizi sanitari regionali (age.na.s), Italy ; 2013. [cited 24 October 2021]. Available from: http://corehta.info/ViewCover.aspx?id=113

Prognostic tests for breast cancer recurrence (uPA/PAI-1 [FEMTELLE], MammaPrint, Oncotype DX )

<< Clinical EffectivenessEthical analysis >>

Costs and economic evaluation

Authors: Isaura Vieira, Mirella Corio, Maria Rosaria Perrini, Matteo Ruggeri

Summary

Based on the literature reviewed, the introduction of prognostic tests into the clinical pathway of women with early invasive breast cancer could bring a positive impact on the management, treatment costs and quality of life due to more appropriate treatment following better prognostic testing. In other words, the introduction of these tests may avoid unnecessary use of expensive chemotherapy with its associated adverse effects for women who derive little or no benefit from it and may reduce the mortality rate in high-risk women who would have benefitted from chemotherapy {13}.

We do not yet have enough information to reach conclusions about the cost-effectiveness ratios. Further generation of effectiveness data may make the estimation of such ratios possible in the future.

Introduction

The results of prognostic  tests for breast cancer recurrence (PTBCRs) can influence further therapeutic decisions about the use of adjuvant chemotherapy to treat women diagnosed with early stage invasive breast cancer. However these tests are more costly than current practice (St Gallen consensus recommendations, National Comprehensive Cancer Network guidelines (NCCN), Adjuvant! Online, and Nottingham Prognostic Index (NPI)). The aim of the costs and economic evaluation domain is to determine whether the use of the PTBCRs (uPA/PAI-1[FEMTELLE®], MammaPrint®, Oncotype DX®) is a cost-effective option, taking into consideration both the clinical outcomes (for example, patient morbidity, mortality and/or quality of life) and the costs/resources used.

The costs and economic evaluation domain consists of five topics: cost-effectiveness, resource utilisation, unit costs, indirect costs and outcomes/consequences.

According to the findings of the clinical effectiveness domain {EFF domain}, there was insufficient good quality evidence to determine whether using these PTBCRs to guide the use of adjuvant chemotherapy effectively improves long term clinical outcomes. The EFF domain found a few studies of very low quality that assessed the predictive ability of the tests. In the absence of an accurate estimate of the clinical value of the tests, it was not possible to estimate cost effectiveness and only a rough description has been provided of how an economic evaluation would be prepared if clinical effectiveness data were to become available.

Methodology

Frame

The collection scope is used in this domain.

TechnologyuPA/PAI-1 (FEMTELLE), MammaPrint, Oncotype DX
Description

Urokinase plasminogen activator /plasminogen activator inhibitor 1 ELISA (uPA/PAI-1) is a registered enzyme-linked immunoassay (ELISA) kit (FEMTELLE) for the analysis of uPA/PAI-1 in fresh frozen tissue and is being provided by American Diagnostica Inc. It is CE marked in Europe but for research use only in the USA. Other commercial ELISA kits for separate in-house analysis of uPA and/or PAI-1 are available from different suppliers. These also use samples other than tissue and are also used for indications other than cancer {1}.

Technical details:

- Inspection of unfixed tissue

- Removal of a representative piece of tumour tissue (>50 mg)

- Freezing of the unfixed tissue (-20°C or colder)

- Storage of the frozen tissue (-20°C or colder) possible up to 3 weeks

Clinical Laboratory (Pathology, Hospital)

- Transport of frozen tumour tissue on dry ice

- Extraction of uPA and PAI-1

- Perform FEMTELLE uPA/PAI-1 ELISA

- Transfer of test results to physician

Costs for FEMTELLE including preparation, shipping and analysis of samples in a qualified laboratory amount to €400 (http://www.hkk.de/info/aktuelles/brustkrebs_tumorprognosetest). In house analysis with separate ELISA kits costs about €200.

Possible logistic issues to consider are {2}:

- Relatively large samples are needed. Given that the mean tumour size is <2 cm in many centres, this means that a substantial part of the tissue may be lacking for light microscopic investigation.

- Many centres no longer routinely freeze breast tissue and therefore lack the expensive equipment for this process.

Oncotype DX (Genomic Health) quantifies gene expression for 21 genes in breast cancer tissue by real-time reverse transcriptase-polymerase chain reaction (RT-PCR).

MammaPrint (Agendia) is a gene expression profiling platform based on microarray technology which uses a 70-gene expression profile {3}. The sample studied is fresh or frozen tissue. It has received 510(k) clearance from the FDA (premarket notification for medical devices), which also covers the use of Asuragen's RNARetain®, a room temperature, molecular fixative that supersedes freezing the tissue before shipment to the central US laboratory (www.agendia.com).

The test requires a fresh sample of tissue  composed of a minimum of 30% malignant cells and must be received by the company in their kit within 5 days of obtaining the material. The MammaPrint assay was developed on the basis of research initially conducted at the Netherlands Cancer Institute (Amsterdam) and collaborating institutions. Primary tumours from 117 patients with axillary lymph node-negative primary breast cancer were analysed on oligonucleotide microarrays. The data were subjected to supervised classification to establish a 70-gene RNA expression profile that correlated with a relatively short interval to distant metastases. [from NICE protocol and ASCO guideline]

Oncotype DX and MammaPrint have been evaluated and large-scale studies (TAILORx and MINDACT) are underway. The German Working Group for Gynecological Oncology1 (AGO) and the American Society of Clinical Oncology (ASCO) have recommended uPA/PAI-1 as risk-group-classification markers for routine clinical decision making in node-negative breast cancer, alongside established clinical and histomorphological factors.

Oncotype DX is recommended for node negative, oestrogen receptor-positive women and MammaPrint is applied in all early breast cancers. The tests are expensive: MammaPrint costs €2675 and Oncotype DX, US $3400.

RT-PCR and microarray analysis usually cost US $3500 or more. Oncotype and MammaPrint are not routinely covered by German statutory health insurance. MammaPrint is covered by Medicare and Medicaid in the USA (Pharmacogenomics Reporter: 23 December 2009; www.genomeweb.com.)

MeSH Terms:

There are no MeSH-Terms for Oncotype DX and MammaPrint.

Intended use of the technologyDefining an existing health condition in further detail to assist selection of appropriate or optimal treatment

Assessment of risk of breast cancer recurrence

Target condition
Breast cancer recurrence
Target condition description

Assessment of risk of breast cancer recurrence and likelihood of benefit from adjuvant treatment (particularly chemotherapy).

As testing for oestrogen receptor positivity is already considered to be part of the standard of care using these tests to decide on adjunctive treatment with Tamoxifen will not be considered part of the study question.

Target population

Target population sex: Female. Target population age: Any age except fetuses. Target population group: Patients who have the target condition.

Target population description

Women with invasive breast cancer in whom adjunctive treatment might be indicated

ComparisonStandard of care
Description

Standard care without any of the three index tests (uPA/PAI-1, MammaPrint, Oncotype DX).

Depending on manpower and time resources the three index tests may also be compared with each other.

Assessment elements

TopicIssue RelevantResearch questions or rationale for irrelevance
E0001Resource utilizationWhat types of resources are used when delivering the assessed technology and its comparators (resource use identification)?yesWhat types of resources are used when delivering uPA/PAI-1 (Femtelle), OncotypeDx™ or MammaPrint® and what types of resources are used when delivering standard clinical practice?
E0002Resource utilizationWhat amounts of resources are used when delivering the assessed technology and its comparators (resource use measurement)?yesWhat quantity of resources is used when delivering uPA/PAI-1 (Femtelle), OncotypeDx™ or MammaPrint® and what quantity of resources are used when delivering standard clinical practice?
E0003Unit costsWhat are the unit costs of the resources used when delivering the assessed technology and its comparators?yesWhat are the unit costs of the resources used when delivering uPA/PAI-1 (Femtelle), OncotypeDx™ or MammaPrint® and what are the unit costs of the resources used when delivering standard clinical practice?
E0004Indirect CostsWhat is the impact of the technology on indirect costs?yesWhat is the impact of uPA/PAI-1 (Femtelle), OncotypeDx™ or MammaPrint® on indirect costs?
E0005OutcomesWhat are the incremental effects of the technology relative to its comparator(s)?yesWhat are the incremental effects of uPA/PAI-1 (Femtelle), OncotypeDx™ or MammaPrint® relative to standard clinical practice?
E0006Cost-effectivenessWhat is the incremental cost-effectiveness ratio?yesWhat is the incremental cost-effectiveness ratio of uPA/PAI-1 (Femtelle), OncotypeDx™ or MammaPrint® compared to standard clinical practice?

Methodology description

Domain frame

The project scope is applied in this domain and we have added the time frame and perspective to the economic analysis:

Target population

Women with early invasive breast cancer

Intervention

Use of at least one of the following prognostic tests: uPA/PAI-1 (FEMTELLE), MammaPrint or Oncotype DX

Comparators

Standard care without any of the three index tests (uPA/PAI‐1 [FEMTELLE], MammaPrint, Oncotype DX). As currently there is no standard universally accepted practice, different practices may be involved such as testing with St Gallen consensus recommendations, NCCN guidelines , Adjuvant! Online, or the NPI

Outcomes

Quality-adjusted life years (QALY)

(morbidity and mortality or survival, safety [adverse events according adjuvant chemotherapy], quality of life, clinical decision making on treatment choice with adjuvant chemotherapy, patient satisfaction, overall benefit and harms in health outcomes)

Time frame

Until the end of life

Perspective

Consequences and costs are assessed from the societal perspective

Information sources

The information sources and search strategy were contained in the one adopted for the Core HTA {Appendix COL-1}. Of the 616 articles identified, 61 studies were identified for use in this domain by one reviewer who used the following search terms alone included in the title and abstract of each article: “resource”, “cost”, “impact” and “effectiveness”. The 61 studies identified were divided among four reviewers for a second review based on the abstract and using the following inclusion criteria:

  • abstracts that referred to the project scope (PICO description above);
  • abstracts that referred to domain-specific issues (identification and quantification of resources, existence of economic model, reference to indirect costs, treatment guidelines);
  • studies presented in conferences or meetings that were only available in abstract or poster format were excluded.

18 of the 61 papers were selected, divided among the four reviewers and the data were extracted by each reviewer.

The authors of the studies presented in conferences or meetings and that were only available in abstract or poster format were contacted to request information about the status of the study. All authors successfully contacted responded that their studies had not been published and that there had been no further developments.

A specific search of the National Institute for Health and Clinical Excellence (NICE) website was also performed to identify guidance concerning the treatment of early invasive breast cancer.

uPA/PAI-1 (FEMTELLE)

The search did not identify any economic studies.

MammaPrint

The search identified three economic studies. Chen et al. {6} compared MammaPrint with Adjuvant! Online. Eng-Wong et al. {10} used Oncotype DX and Adjuvant! Online. Retel et al. {5} compared MammaPrint with St Gallen consensus recommendations and Adjuvant! Online.

Oncotype DX

The search identified nine economic studies. Bacchi et al. {9} compared Oncotype DX with standard care (data collected from a survey of doctors). Eng-Wong et al. {10} used MammaPrint and Adjuvant! Online. Vanderlaan et al. {7} and Hornberger et al. {8} used NCCN as comparator. Tsoi et al. {4} used Adjuvant! Online as comparator. Kondo et al. {2,3} compared Oncotype DX with NCCN and St Gallen consensus. Klang et al. {1} and Kelly et al. {11} did not identify the comparator used in their studies.

Quality assessment tools or criteria

Quality assessment criteria were not applied to the studies that were identified for review. The quality assessment of economic studies could be done using Drummond's criteria {12} although we have decided not to use it here as there were few studies and all the information available was required.

Analysis and synthesis

Data from the different studies were not synthesised as this was not necessary for this domain. The studies were compared, however, to identify any differences in study methodology.

Result cards

Resource utilization

Result card for ECO1: "What types of resources are used when delivering uPA/PAI-1 (Femtelle), OncotypeDx™ or MammaPrint&#174; and what types of resources are used when delivering standard clinical practice?"

View full card
ECO1: What types of resources are used when delivering uPA/PAI-1 (Femtelle), OncotypeDx™ or MammaPrint&#174; and what types of resources are used when delivering standard clinical practice?
Method
Frame
Result
Comment

Importance: Critical

Transferability: Completely

Result card for ECO2: "What quantity of resources is used when delivering uPA/PAI-1 (Femtelle), OncotypeDx™ or MammaPrint&#174; and what quantity of resources are used when delivering standard clinical practice?"

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ECO2: What quantity of resources is used when delivering uPA/PAI-1 (Femtelle), OncotypeDx™ or MammaPrint&#174; and what quantity of resources are used when delivering standard clinical practice?
Method
Result

Importance: Critical

Transferability: Partially

Unit costs

Result card for ECO3: "What are the unit costs of the resources used when delivering uPA/PAI-1 (Femtelle), OncotypeDx™ or MammaPrint&#174; and what are the unit costs of the resources used when delivering standard clinical practice?"

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ECO3: What are the unit costs of the resources used when delivering uPA/PAI-1 (Femtelle), OncotypeDx™ or MammaPrint&#174; and what are the unit costs of the resources used when delivering standard clinical practice?
Method
Result

Importance: Critical

Transferability: Not

Indirect Costs

Result card for ECO4: "What is the impact of uPA/PAI-1 (Femtelle), OncotypeDx™ or MammaPrint&#174; on indirect costs?"

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ECO4: What is the impact of uPA/PAI-1 (Femtelle), OncotypeDx™ or MammaPrint&#174; on indirect costs?
Method
Result
Comment

Importance: Optional

Transferability: Not

Outcomes

Result card for ECO5: "What are the incremental effects of uPA/PAI-1 (Femtelle), OncotypeDx™ or MammaPrint&#174; relative to standard clinical practice?"

View full card
ECO5: What are the incremental effects of uPA/PAI-1 (Femtelle), OncotypeDx™ or MammaPrint&#174; relative to standard clinical practice?
Method
Result
Comment

Importance: Critical

Transferability: Completely

Cost-effectiveness

Result card for ECO6: "What is the incremental cost-effectiveness ratio of uPA/PAI-1 (Femtelle), OncotypeDx™ or MammaPrint&#174; compared to standard clinical practice?"

View full card
ECO6: What is the incremental cost-effectiveness ratio of uPA/PAI-1 (Femtelle), OncotypeDx™ or MammaPrint&#174; compared to standard clinical practice?
Method
Result
Comment

Importance: Critical

Transferability: Partially

Discussion

Due to the lack of high quality evidence to identify the effectiveness of the tests compared with standard care {EFF domain}, it was not possible to compute the cost-effectiveness ratios or to provide the information requested in the result cards. The main objective has been to present a rough description of what could be used when new evidence becomes available.

As described in the section on domain methodology, quality criteria were not applied to the studies identified for review. The impact of the information obtained from the literature used is unknown. In future evaluation efforts, it is important to assess the quality of economic studies using, for example, the Drummond’s criteria {12}. It has been noted that the economic studies provided differing results. It is not possible to conclude whether these differences result from differences in study quality, or from the variations in prices in different countries, or from the different perspectives used in the studies.

Further research will be needed in order to generate more evidence and to increase the certainty of almost all of the domain assessment elements.

References

  1. Klang SH, Hammerman A, Liebermann N, Efrat N, Doberne J, Hornberger J. Economic implications of 21-gene breast cancer risk assay from the perspective of an Israeli-managed health-care organization. Value in Health. 2010; 13(4).
  2. Kondo M, Hoshi SL, Ishiguro H, Yoshibayashi H, Toi M. Economic evaluation of 21-gene reverse transcriptase-polymerase chain reaction assay in lymph-node-negative, estrogen-receptor-positive, early-stage breast cancer inJapan. Breast cancer research and treatment. 2008; 112(1): 175-187.
  3. Kondo M, Hoshi SL, Yamanaka T, Ishiguro H, Toi M. Economic evaluation of the 21-gene signature (Oncotype DX) in lymph node-negative/positive, hormone receptor-positive early-stage breast cancer based on Japanese validation study (JBCRG-TR03). Breast cancer research and treatment. 2011; 127(3): 739-749.
  4. Tsoi DT, Inoue M, Kelly CM, Verma S, Pritchard KI. Cost-effectiveness analysis of recurrence score-guided treatment using a 21-gene assay in early breast cancer. Oncologist. 2010; 15(5): 457- 465.
  5. Retel VP, Joore MA, Knauer M, Linn SC, Hauptmann M, Harten WH. Cost-effectiveness of the 70-gene signature versus St. Gallen guidelines and Adjuvant Online for early breast cancer. European Journal of Cancer. 2010; 46(8): 1382 - 1391.
  6. Chen E, Tong KB, Malin JL. Cost-effectiveness of 70-gene MammaPrint signature in node-negative breast cancer. American Journal of Managed Care. 2010 December; 16(12): e333-e342.
  7. Vanderlaan BF, Broder MS, Chang EY, Oratz R, Bentley TG. Cost-effectiveness of 21-gene assay in node-positive, early-stage breast cancer. American Journal of Managed Care. 2011 July; 17(7): 455- 464.
  8. 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. American Journal of Managed Care. 2005 May; 11(5): 313 – 324.
  9. Bacchi CE, Prisco F, Carvalho FM, Ojopi EB, Saad ED. Potential economic impact of the 21-gene expression assay on the treatment of breast cancer inBrazil. Revista da Associacao Medica Brasileira. 2010; 56(2): 186 – 191.
  10. Eng-Wong J, Isaacs C. Prediction of benefit from adjuvant treatment in patients with breast cancer. Clinical Breast Cancer. 2010 June; 10, Supplement 1: E32-E37.
  11. Kelly CM, Warner E, Tsoi DT, Verma S, Pritchard KI. Review of the clinical studies using the 21-gene assay. Oncologist. 2010; 15(5): 447 – 456.
  12. Drummond M, O’Brien B, Stoddart GL, TorranceGW. Methods for the economic evaluation of health care programs. Second edition.United States:OxfordUniversityPress; 1997
  13. NICE. Gene expression profiling and expanded immunohistochemistry tests to guide the use of adjuvant chemotherapy in breast cancer management: MammaPrint, Oncotype DX, IHC4 and Mammostrat - Diagnostics consultation document [Internet]. 2012 January. Available from: http://www.nice.org.uk/nicemedia/live/13283/58040/58040.pdf

Appendices

APPENDIX ECO-1. Study cards for costs and economic evaluation domain

Author

Tsoi DT, Inoue M, Kelly CM, Verma S, Pritchard KI.

 

Year

2010

 

Study title

Cost-effectiveness analysis of recurrence score-guided treatment using a 21-gene assay in early breast cancer.

 

Study objective

to compare the cost-effectiveness of treatment guided either by 21-gene assay or by Adjuvant! Online program

 

Study design

Markov model

 

Study methodology

Is in the article

Population (target)

50-year-old woman with lymph node-negative HR-positive breast cancer

 

Intervention (genetic test for cancer)

recurrence score (RS)-guided treatment using 21-gene assay

 

Comparator

Adjuvant! Online program

 

Clinical outcomes (source)

Literature

 

Types of resources used (source of information)

- for tests

- for standard practice

healthcare payer's perspective with results reported in 2008 Canadian dollars ($).

 

Quantity of resources used (source of information)

- for tests

- for standard practice

Event rates, costs, and utilities were derived from the literature

 

Unit costs of resources used (source of information)

- for tests

- for standard practice

Canadian dollars

 

Types of costs (source of information):

- Direct costs (to distinguish between for tests and for standard practice)

- Indirect costs (to distinguish between for tests and for standard practice)

Direct costs

 

Are chemotherapy regimens identified? (treatment decided based on tests results)

Women classified to be at high risk all received chemotherapy followed by tamoxifen and those classified to be at low risk received tamoxifen only.

 

Modelling structure of economic analysis (CEA, CUA, etc)

Cost effectiveness analysis

 

Effectiveness measure (LY, QALY,…)

QALY

 

Cost/effectiveness ratio (ICER)

For a 50-year-old woman, RS-guided treatment was associated with an incremental lifetime cost of $4,102 and a gain in 0.065 QALY, with an ICER of $63,064 per QALY compared with AOL-guided treatment.

 

Description of adverse events considered (stratified by treatment arm or stated)

Yes, stratified

 

Author conclusions

The 21-gene assay appears cost-effective from a Canadian healthcare perspective.

 

Author disclosure (conflict of interest)

no

 
  

Author

Retel VP, Joore MA, Knauer M, Linn SC, Hauptmann M, Harten WH

 

Year

2010

 

Study title

Cost-effectiveness of the 70-gene signature versus St. Gallen guidelines and Adjuvant Online for early breast cancer.

 

Study objective

To assess the cost effectiveness of the 70-gene signature (MammaPrint) prognostic test to guide adjuvant treatment decisions in patients with node-negative breast cancer.

 

Study design

Markov model to simulate the 20-year costs and outcomes (survival and quality-of-life adjusted survival (QALYs))

 

Study methodology

Is in the article

 

Population (target)

a hypothetical cohort of node-negative, oestrogen receptor positive breast cancer patients.

 

Intervention (genetic test for cancer)

70-gene signature

 

Comparator

St. Gallens guidelines and Adjuvant Online Software

 

Clinical outcomes (source)

Sensitivity and specificity

 

Types of resources used (source of information)

- for tests

- for standard practice

pooled analysis consisting of 305 tumour samples from 3 previously reported validation studies concerning the 70-gene signature

 

Quantity of resources used (source of information)

- for tests

- for standard practice

Literature

 

Unit costs of resources used (source of information)

- for tests

- for standard practice

Health Care Insurance Board. Pharmacotherapeutic Compass

(in Dutch), 2006

 

Types of costs (source of information):

- Direct costs (to distinguish between for tests and for standard practice)

- Indirect costs (to distinguish between for tests and for standard practice)

Direct costs, literarue

 

Are chemotherapy regimens identified? (treatment decided based on tests results)

Yes

 

Modelling structure of economic analysis (CEA, CUA, etc)

Markov model, Cost effectiveness analysis

 

Effectiveness measure (LY, QALY,…)

QALY

 

Cost/effectiveness ratio (ICER)

the 70-gene signature has the highest probability of being cost-effective for a willingness to pay for a QALY higher than €12.000.

 

Description of adverse events considered (stratified by treatment arm or stated)

NA

 

Author conclusions

the 70-gene signature improves quality-adjusted survival and has the highest probability of being cost-effective.

 

Author disclosure (conflict of interest)

NA

 
       
 

Author

Er Chen, MPP; Kuo Bianchini Tong, MS; and Jennifer L. Malin, MD, PhD

Year

2010

Study title

Cost-effectiveness of 70-gene MammaPrint signature in node-negative breast cancer

Study objective

Evaluate the cost-effectiveness of 70-gene MammaPrint signature vs Adjuvant! Online software  in patients 60 years or younger with early-stage breast cancer.

Study design

Cost-effectiveness and cost-utility analyses from a US payer perspective

Study methodology

Is in the article / Is not in the article

Population (target)

Patients 60 years or younger with ER-independent, T1 or T2, lymph node-negative tumours.

Intervention (genetic test for cancer)

70-Gene MammaPrint Signature (Agendia Inc, Huntington Beach, CA)

Comparator

Adjuvant! Online software

Clinical outcomes (source)

risk classification and 10-year overall survival

(Buyse M, Loi S, van’t Veer L, et al; TR ANSBIG Consortium. Validation and clinical utility of a 70-gene prognostic signature for women with node-negative breast cancer. J Natl Cancer Inst. 2006; 98(17):1183-1192)

Types of resources used (source of information)

- for tests

- for standard practice

cost of risk classification, adjuvant endocrine therapy, adjuvant chemotherapy, administration, treatment-related toxic effects, and breast cancer surveillance, treating local recurrence or distant recurrence, terminal care for cancer-related death, terminal care for patients without cancer

(literature)

Quantity of resources used (source of information)

- for tests

- for standard practice

Not identified

Unit costs of resources used (source of information)

- for tests

- for standard practice

Not identified

(literature)

Types of costs (source of information):

- Direct costs (to distinguish between for tests and for standard practice)

- Indirect costs (to distinguish between for tests and for standard practice)

Direct costs

Are chemotherapy regimens identified? (treatment decided based on tests results)

No

Modelling structure of economic analysis (CEA, CUA, etc)

Cost-effectiveness and cost-utility

Effectiveness measure (LY, QALY,…)

LY and QALY

Cost/effectiveness ratio (ICER)

$10,000 per LY or QALY

Description of adverse events considered (stratified by treatment arm or stated)

chemotherapy-related serious adverse events

Author conclusions

The model results suggest that treatment guided by 70-gene signature may be associated with an increase in the mean life expectancy and a slight increase in cost. The ICER of approximately $10,000 per LY or QALY for the base case is well within the range of value generally considered cost-effective for a diagnostic or therapeutic intervention and is substantially lower than ICERs reported in the literature for other oncology therapies.

Our study findings suggest that the use of this test is highly cost-effective among ER-positive patients but is less so among ER-negative patients. In addition, the clinical and economic trade-offs of using the test in postmenopausal women need further evaluation.

Author disclosure (conflict of interest)

Author Affiliations: From Quorum Consulting, Inc (EC, KBT), San Francisco, CA; and the Department of Medicine (JLM), University of California at Los Angeles, Los Angeles, CA.

Funding Source: Funding for this study was provided through an unrestricted grant from Agendia Inc.

Author Disclosures: Ms Chen and Mr Tong report being employees of Quorum Consulting, which received payment from Agendia for the preparation of the manuscript. Dr Malin reports serving as a paid consultant to Quorum and receiving payment for her involvement in the preparation of this manuscript.

 

Author

Vanderlaan BF, Broder MS, Chang EY, Oratz R, Bentley TG.

Year

2011

Study title

Cost-effectiveness of 21-gene assay in node-positive, early-stage breast cancer

Study objective

To assess impact on health outcomes and healthcare expenditures of adopting a 21-gene assay

Study design

deterministic decision-analytic model

Study methodology

Is in the article

Population (target)

women with early-stage, minimally node-positive, oestrogen receptor-positive (N (1-3)/ER) HER2-negative breast cancer

Intervention (genetic test for cancer)

care determined by the 21-gene assay recurrence score

Comparator

Usual care/ chemotherapy

Clinical outcomes (source)

Annual numbers of events were multiplied by quality-adjusted life-years (QALYs) lost

Types of resources used (source of information)

- for tests

- for standard practice

costs and quality-of-life outcomes, chemotherapy, adverse events, supportive care, recurrence, and second primary cancers for usual care

Quantity of resources used (source of information)

- for tests

- for standard practice

Literature, national statistics, physician surveys, and Medicare Part B prices.

Unit costs of resources used (source of information)

- for tests

- for standard practice

managed care payer perspective for the US population.. US dollars

Types of costs (source of information):

- Direct costs (to distinguish between for tests and for standard practice)

- Indirect costs (to distinguish between for tests and for standard practice)

Direct costs

Are chemotherapy regimens identified? (treatment decided based on tests results)

yes

Modelling structure of economic analysis (CEA, CUA, etc)

Cost effectiveness

Effectiveness measure (LY, QALY,…)

QALY

Cost/effectiveness ratio (ICER)

Patients receiving the assay were predicted to gain 0.127 QALY and save $4359 annually from avoiding chemotherapy, adverse events, supportive care, and secondary primary tumours. Although overall results were sensitive only to reduced impact of testing and chemotherapy costs, they were still highly cost-effective (incremental cost-effectiveness ratio <$20,000/QALY).

Description of adverse events considered (stratified by treatment arm or stated)

Yes, stratified by treatment arm

Author conclusions

Use of a 21-gene assay in patients with early-stage N (1-3)/ER HER2-negative breast cancer may improve health outcomes and add no incremental cost, thereby providing valuable insight for health plans, the Centers for Medicare and Medicaid Services, and clinicians regarding coverage policies and treatment decisions.

Author disclosure (conflict of interest)

No

    
 

Author

Carlos Eduardo Bacchi1*, Flavio Prisco2, Filom ena M. Carvalho3, Elida B. Ojopi4, Everardo D. Saad5

Year

2010

Study title

Potential economic impact of the 21-gene expression assay on the treatment of breast cancer in Brazil

Study objective

investigate the potential impact of incorporating the 21-gene expression assay into private practice in Brazil, from the perspective of third party payers.

Study design

web-based survey with 30 (of a total of approximately 700) Brazilian medical oncologists, stratified by State according to the proportion of patients with breast cancer and private health insurance and not aware of the study objective

The questionnaire consisted of case vignettes presenting different clinical scenarios aiming to investigate the treatment of first choice for patients with axillary-node negative, oestrogen-receptor-positive, early breast cancer, regardless of menopausal status.

Responses allowed a quantitative assessment of the care patterns regarding chemotherapy regimen for each of the four tumour sizes. In addition, we assessed interviewees’ preferences regarding the type and dose of antiemetic premedication used in each case, the dose and duration of use of granulocyte colony-stimulating factor (G-CSF) and antibiotics for in-hospital treatment of febrile neutropenia, should it develop.

In each subgroup of patients defined by tumour size in the hypothetical cohort with no access to the 21-gene expression assay, the proportion of patients receiving chemotherapy, as well as regimens used in each subgroup, were derived from the survey with medical oncologists.

The model assumed that patients with access to the 21-gene expression assay would receive chemotherapy if their recurrence score was intermediate or high, whereas patients with a low score would not receive chemotherapy.

The model followed the perspective of private third party payers, and incorporated only the direct medical expenses associated with treatment.

Study methodology

Is in the article

Population (target)

Patients with axillary-node negative, oestrogen-receptor-positive, early breast cancer, regardless of menopausal status

Intervention (genetic test for cancer)

21-gene expression

Comparator

Not identified – standard practice based on the survey

Clinical outcomes (source)

Not identified

Types of resources used (source of information)

- for tests

- for standard practice

Only identified the resources associated with chemotherapy, based on the survey and the tests

Quantity of resources used (source of information)

- for tests

- for standard practice

The number of cycles of chemotherapy and type of drugs used were identified, but not quantified.

Unit costs of resources used (source of information)

- for tests

- for standard practice

Costs were calculated using the manufacturer’s recommended prices

Types of costs (source of information):

- direct costs (to distinguish between for tests and for standard practice)

- indirect costs (to distinguish between for tests and for standard practice)

Direct medical expenses assessed in the study were costs of chemotherapy, antiemetic premedication, prophylactic or therapeutic G-CSF, and antibiotics for in-hospital treatment of febrile neutropenia and the cost of the test.

Other direct medical costs, indirect medical costs, and non-medical costs were not considered in the model.

Are chemotherapy regimens identified? (treatment decided based on tests results)

Yes (yes)

Different regimen depending on the tumour size

Modelling structure of economic analysis (CEA, CUA, etc)

Cost analysis

Effectiveness measure (LY, QALY,…)

Not measured

Cost/effectiveness ratio (ICER)

not calculated

Description of adverse events considered (stratified by treatment arm or stated)

incidence of febrile neutropenia associated with the regimens

(stratified by treatment arm)

Author conclusions

Results of our study suggest that the 21-gene expression assay would be a cost-saving in Brazil, from the perspective of third-party payers and considering the current price for the test in Brazil. However, results also suggest that testing could actually increase direct medical costs in patients with lymph node negative, oestrogen-receptor-positive T1 tumours, and reduce costs in patients with tumour size >2 cm.

The model included the main financial costs associated with adjuvant therapy for breast cancer, but many other direct costs, as well as indirect costs, were not taken into account by the model. In addition, the effectiveness of therapy based on risk prediction by the 21-gene expression assay was not considered in the model.

Author disclosure (conflict of interest)

None

 

Author

Jennifer Eng-Wong, Claudine Isaacs

Year

2010

Study title

Prediction of benefit from adjuvant treatment in patients with breast cancer

Study objective

review the clinical tools that are commonly used as well as those under development and the clinical trials in which they are being further evaluated to better determine which tumours will benefit from chemotherapy

Study design

Descriptive analysis to

Study methodology

Is not in the article

Population (target)

Not applicable

Intervention (genetic test for cancer)

Not applicable

Comparator

Adjuvant!, Oncotype DX, and MammaPrint

Clinical outcomes (source)

Not applicable

Types of resources used (source of information)

- for tests

- for standard practice

Not applicable

Quantity of resources used (source of information)

- for tests

- for standard practice

Not applicable

Unit costs of resources used (source of information)

- for tests

- for standard practice

Not applicable

Types of costs (source of information):

- Direct costs (to distinguish between for tests and for standard practice)

- Indirect costs (to distinguish between for tests and for standard practice)

Not applicable

Are chemotherapy regimens identified? (treatment decided based on tests results)

Not applicable

Modelling structure of economic analysis (CEA, CUA, etc)

Not applicable

Effectiveness measure (LY, QUALY,)

Not applicable

Cost/effectiveness ratio (ICER)

Not applicable

Description of adverse events considered (stratified by treatment arm or stated)

Not applicable

Author conclusions

Significant advances in molecular biology and the foresight to maintain tumour specimens in the clinical trial setting have led to major improvements in selecting appropriate candidates for adjuvant chemotherapy, in particular those with hormone receptor–positive, node-negative cancer. For hormone receptor–negative and more advanced disease, clinicians typically use adjuvant chemotherapy; however, treatment choices are expected to be better informed based on incorporation of molecular profiling analyses into current trials.

Author disclosure (conflict of interest)

Not identified

   

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