2/11/2014

Perspectives with Prognostic and Predictive Factors

William Fraser Symmans, MD Professor, Pathology University of Texas MD Anderson Cancer Center

Dr. Symmans has financial relationships with commercial interests that produce healthcarerelated products or services relevant to the content I am planning, developing presenting with Amgen, Nuevra Biosciences and ISIS Pharmaceuticals.

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2/11/2014

Best of SABCS 2013 Perspectives With Prognostic and Predictive Factors W. Fraser Symmans, M.D. Professor Director of Research Operations Department of Pathology UT M.D. Anderson Cancer Center

Disclosures

Nuvera Biosciences, Inc.

Co-founder and scientific advisor

Amgen ISIS Pharmaceuticals

Stock Stock

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2/11/2014

Prognosis With Endocrine Therapy Postmenopausal women 21-gene recurrence score

Nodal Status Matters

r

Hazard ratio for RS group was adjusted for tumor size, grade, age, and treatment Dowsett et al JCO 2010;28:1829-34

Prediction From Adjuvant Treatment Trials Test Result = Negative

Treatment A Treatment B

Test Result = Positive

Treatment A Treatment B

Significant interaction between test result and the relative survival outcomes between treatment A and treatment B

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2/11/2014

Prediction of Chemotherapy Response and Survival Response

Absolute Risk

NAC

Model depends on alignment of BOTH the predicted response outcome and the absolute survival probability

San Antonio Breast Cancer – Cancer Therapy and Research Center at UT Health Science Center – December 10-14, 2013

Prediction of late distant recurrence after 5 years of endocrine treatment: A combined analysis of 2137 patients from the ABCSG-8 and transATAC studies using the PAM50 Risk of Recurrence (ROR) score Ivana Sestak Jack Cuzick, Mitch Dowsett, Martin Filipits, Peter Dubsky, J. Wayne Cowens, Sean Ferree, Carl Schaper, Christian Fesl, Michael Gnant Centre for Cancer Prevention, Wolfson Institute of Prevention Medicine, Queen Mary University, London, UK Academic Department of Biochemistry, Royal Marsden Hospital, London, UK Austrian Breast and Colorectal Cancer Study Group, Vienna, Austria Department of Surgery and Comprehensive Cancer Centre, Medical University of Vienna, Vienna, Austria NanoString Technologies, Seattle, WA, USA MyRAQA, Redwood Shores, CA, USA This presentation is the intellectual property of the author/presenter. Contact them at [email protected] for permission to reprint and/or distribute.

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2/11/2014

San Antonio Breast Cancer – Cancer Therapy and Research Center at UT Health Science Center – December 10-14, 2013

Background • PAM50

ROR =aRLumA+

- 50-gene test developed to identify the intrinsic breast cancer subtypes (luminal A/B, HER2-enriched, Basal-like) (Parker et al, JCO, 2009, 27, 1160; Nielsen et al, CCR, 2010, 16, 5222)

bRLumB+

Pearson’s correlation to centroids

cRHer2e+ dRBasal+ eP+

Proliferation score (19 genes)

fT

Tumor size

 ROR score using 46 gene signature including tumour size (excluded BIRC5, MYBL2, GRB7, CCNB1)

• Clinical Treatment Score (CTS) - Nodal status, grade, tumour size, age, treatment - Developed on transATAC data set This presentation is the intellectual property of the author/presenter. Contact them at [email protected] for permission to reprint and/or distribute.

San Antonio Breast Cancer – Cancer Therapy and Research Center at UT Health Science Center – December 10-14, 2013

Objectives

• Primary: - Assess ability of ROR score to predict late distant recurrence in patients recurrence free after 5 years of endocrine treatment

This presentation is the intellectual property of the author/presenter. Contact them at [email protected] for permission to reprint and/or distribute.

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2/11/2014

San Antonio Breast Cancer – Cancer Therapy and Research Center at UT Health Science Center – December 10-14, 2013

Patients characteristics transATAC (N=862)

ABCSG-8 (N=1275)

10.0 (9.1-10.1)

10.3 (8.8-12.4)

Age > 65 years

41.5%

39.3%

Node positive

24.9%

26.8%

19.0 (10.1)

16.7 (8.3)

Well

195 (22.6%)

242 (19.0%)

Moderate

519 (60.2%)

1033 (81.0%)

Poor

148 (17.2%)

-

80 (9.3%)

68 (5.3%)

Median follow-up, years (IQR)

Tumour size, mm (mean, SD) Grade

Distant recurrence

This presentation is the intellectual property of the author/presenter. Contact them at [email protected] for permission to reprint and/or distribute.

San Antonio Breast Cancer – Cancer Therapy and Research Center at UT Health Science Center – December 10-14, 2013

Risk groups – ROR score

15

-

Intermediate (N=538 (25.2%))

3.26 (2.07-5.13)

High (N=416 (19.5%))

6.90 (4.54-10.47)

16.6% 15

8.3%

0

0

2.4%

5

5

10

High Intermediate Low

10

Distant recurrence (%)

Low (N=1183 (55.4%))

20

20

HR (95% CI)

5

6

7 8 Follow-up time [years]

9

10

This presentation is the intellectual property of the author/presenter. Contact them at [email protected] for permission to reprint and/or distribute.

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2/11/2014

San Antonio Breast Cancer – Cancer Therapy and Research Center at UT Health Science Center – December 10-14, 2013

ROR score - multivariate analysis All patients (N=2137)

HR=2.07 (1.63-2.64)

Node negative (N=1580)

HR=2.11 (1.48-3.00)

Node positive (N=557)

HR=2.15 (1.52-3.03)

HER2-negative (N=1974)

HR=2.19 (1.69-2.84)

Node negative/ HER2-negative (N=1455)

HR=2.41 (1.65-3.50)

1

2 Hazard ratio for IQR

5

This presentation is the intellectual property of the author/presenter. Contact them at [email protected] for permission to reprint and/or distribute.

Prognostic information (LRχ2) for distant recurrence in sub-groups (multivariate analysis (scores added to CTS))

Years 0-5

Years 5-10

N0

N+

N0/HER2-

N0

N+

N0/HER2-

IHC4

26.8

0.4

13.5

1.8

5.7

3.6

RS

15.3

0.3

8.0

0.7

5.9

1.6

ROR

10.6

1.1

10.1

9.0

7.2

14.0

BCI

14.9

1.9

13.5

8.6

2.7

10.1

0.05>P-value>0.001, P-value