Use of Oncotype Dx® Testing

Breast SSG meeting 10th July 2015

Dr Rebecca Bowen

Prognostic and predictive markers used in breast cancer management

Prognostic (recurrence risk)Axillary node statusHistologic type/gradeTumour sizePatient ageLymphatic/Vascular invasionER/PR statusHER2 statusNPI/ Adjuvant Online/ NHS PredictGenomic assays: Endopredict

Prosigna uPA PAI1 Oncotype DX®

Predictive (treatment benefit)ER/PR statusHER2 neu statusOncotype DX® test

Predict treatment benefit

Estimate the risk of disease recurrence

Summary

• 2004 Paik et al NEJM publication on validation of Recurrence Score

• April 2010: first conversation with NICE

• Two UK decision impact studies set up

• Private health insurance companies start to reimburse

• May 2011: NICE diagnostics assessment commenced

• September 2013: NICE recommendation (DG10)

• April 2015: NHS patients can access!

The Oncotype DX® AssayThe only multi-gene assay incorporated into all major

guidelines to predict adjuvant chemotherapy benefit in ER+, HER2-

EBCQuantifies risk of recurrence as a continuous variable

and predicts responsiveness to both tamoxifen and chemotherapyNCCN Guidelines®1

>0.5cm, node negative, N1mi

Predicts the risk of recurrence and may be used to identify patients likely to benefit from tamoxifen or chemotherapy

ASCO® Guidelines2

Node negative

Provides additional prognostic and/or predictive information to complement pathology assessment and to predict response to

adjuvant chemotherapy

ESMO3

Node negative

Provides not only prognostic but also predictive information regarding the utility of cytotoxic therapy in addition to endocrine

therapy

St Gallen Consensus4

Node negative, node positive

Recommended as an option for guidance of chemotherapy decisions in patients at intermediate risk* of distant recurrence

NICE5

Node negative

1.NCCN Practice Guidelines in Oncology. V.2.2015.2.Harris L, et al. J Clin Oncol. 2007.3.Senkus E Ann Oncol 2013.4.Goldhirsch A, et al. Ann Oncol. 2013.

5. NICE Diagnostics Guidance DG10 2013. by other decision making tools or protocols

ASCO is a trademark of the American Society of Clinical Oncology. NCCN and NCCN Guidelines are trademarks of the National Comprehensive Cancer Network.

The guidelines do not endorse products or therapies.*Intermediate risk of distant recurrence is defined as NPI score ≥3.4 or at intermediate risk

The Oncotype DX® assay processGenomic Health has processed >500,000 tests from >70 countries; >3,800 tests from the UK

Resultsgeneration

Billing2-3 weeks

Report delivery

Secure online

portal

Extraction

Quantitation

gDNAdetection

Reverse transcription

QPCR

Order entry

Online

Specimen retrieval

Specimenaccessioning

RequestFedEx

Materials return

Order entry Shipping

Pathology

Analytical laboratory

Reportfulfilmen

t

Material return

Pathology review

Histopath

7-10 days

Triple-neg

Node-negative or with

*1 to 3 positive nodes

Newly diagnosed early stage invasive breast cancer

Newly diagnosed early stage invasive breast cancer

Metastatic or locally advanced breast cancer with 4+ positive nodes

HER2-posER-pos,

HER2-neg

The patient is assessed as being at intermediate risk; the decision to prescribe

chemotherapy remains unclear, so that information on the biological features of the cancer provided by the Oncotype DX® assay is likely to help in a predicting the course of

the disease

*Use of the Oncotype DX®

breast cancer assay in the N+ setting validated for post-menopausal patients

Accessed 14 Jan 2014 HER2: Human Epidermal Growth Factor Receptor 2NICE guidance DG10. http://guidance.NICE.org.UK/DG10 ER: Oestrogen receptor

Clinical indication NICE guidance

Node-negative, ER-positive, HER2-negative

Which patients may benefit from the Oncotype DX® Test?

Recurrence Score® results and patient discussion prior to the Oncotype DX® test

Eligible: Intermediate riskNPI >3.4 ≤ 5.4

Low Benefit of CT on Adjuvant! or ≥3% on PREDICT

• RS <18: Chemotherapy not recommended. Endocrine alone

• RS 18-30: Treatment recommendation discussed prior to testing based on individual score

• RS >30: Chemotherapy recommended

Eligible Patient Summary

• All node negative, ER positive, HER2 negative:

– Grade 1: > 70mm– Grade 2: > 20mm– Grade 3: Any size

Change in Recommendations – Choice Study

• Oncologists recommendation changed in 55 (42%) patients

• 43 chemotherapy to no chemotherapy• 12 no chemotherapy to chemotherapy

• Oncologists recommended chemotherapy in 51% patients pre Oncotype DX and 28% post Oncotype DX

• Changes in recommendation were consistent with the Recurrence Score