Testing for Prostate Cancer Agressiveness

clinical summary

Background:• Prostate cancer has a highly variable natural history and accurately assessing the tumor’s

aggressiveness based on clinical and pathologic features is challenging.

• Novel prognostic markers are needed to more precisely guide therapeutic decisions.

• The Prolaris® test measures the activity of cell cycle progression genes in prostate cancer tissue.

• Prolaris has been tested in five distinct cohorts.

Methods: • All studies were retrospective.

• Formalin fixed prostate tissue from men with adenocarcinoma were analyzed.

• The Prolaris score® is calculated by measuring the average RNA expression of 31 cell cycle progression

genes normalized by the average expression of 15 housekeeping genes as quantitated by RT-PCR.

Summary of Prostate Cancer Studies

* Censored at 5 years.

Myriad, the Myriad logo, Prolaris and the Prolaris logo are either trademarks or registered trademarks of Myriad Genetics, Inc., in the United States and other jurisdictions. ©2013, Myriad Genetics GmbH. Not for distribution in USA.

Prolaris®: a novel genetic test for prostate cancer prognosis

Myriad Genetics GmbHLeutschenbachstrasse 958050 ZurichSwitzerland

www.myriad.com

Conclusions:

• Prolaris predicts prostate cancer outcome in multiple patient cohorts and in diverse clinical settings.

• Prolaris provides independent information beyond clinicopathologic variables.

• Prolaris helps to further differentiate aggressive prostate cancer from indolent cancer.

PRO

L/PS

TR/C

UZI

CK/

07/1

3/EN

V1

A prognostic medicine product for prostate cancer.Prolaris® testing assesses prostate cancer aggressiveness in conjunction with other clinical parameters. Prolaris® measures the expression level of genes involved with cell cycle progression (CCP) in tumor specimens to predict disease outcome.

For more information please contact your local Myriad Representative.

Poster presented at the Global Congress on Prostate Cancer 2013

Prolaris®: a novel genetic test for prostate cancer prognosis

Jack Cuzick1, Matthew Cooperberg2, Greg Swanson3, Stephen Freedland4, Julia Reid5, Gabrielle Fisher1, Jerry Lanchbury5, Alexander Gutin5, Marcello Paglione5, Steven Stone5,

Peter Carroll2, Michael Brawer5, and on behalf of the Transatlantic Prostate Group

1. Center for Cancer Prevention, Wolfson Institute of Preventive Medicine, London, UK 2. Department of Urology, UCSF Hellen Diller Family Comprehensive Cancer Center, San Francisco, CA

3. Departments of Radiation Oncology, Urology and Radiology, University of Texas Health Science Center San Antonio, San Antonio, TX 4. Department of Surgery, Durham VA Medical Center and Department of Surgery, Duke University School of Medicine, Durham, NC

5. Myriad Genetics, Inc. , Salt Lake City, UT

Study Title Sample Type Number of Patients (events)

Event Reference

Biopsy 337 (76) death from prostate cancer Cuzick et al. Lancet Oncology 2011;12(3):245-55.

Cuzick et al. Lancet Oncology 2011;12(3):245-55.

Cooperberg et al. Journal of Clinical Oncology 2013;31:1428-34.

Freedland et al. 2013; In Press.

Cuzick et al. British Journal of Cancer 2012;106:1095-99.

biochemical recurrence

death from prostate cancer

biochemical recurrence

biochemical recurrence*

353 (132)

349 (90)

413 (83)

141 (19)

TURP conservatively managed

Rad prostatectomy 1

Rad prostatectomy 2

External beam Xrt

Needle biopsy conservatively managed

Biopsy

Biopsy

Surgical tumor

Surgical tumor

Results:• Prolaris was a highly significant predictor of outcome in all five studies.

• Prolaris was the dominant predictor in all but one of the studies in multivariate analysis.

• In all five studies, the hazard ratios (HRs) per unit of change in the Prolaris score were remarkably

similar, ranging from 1.97 to 2.92.

• These HRs indicate that the effect size for the Prolaris score is robust in varying clinical settings.

Kaplan Meier Curves

Distribution of Prolaris Scores

Results for Prolaris Score and Gleason Score in Cox PH Models

Multivariate Models

Pearson Correlation Coefficients*

Study Title

Study Title

Hazard Ratio

Hazard Ratio

Type

Gleason Score p-value

95% CI

95% CI

p-value

p-value

p-value

Covariates

Univariate

Multivariate†

Gleason Score

2.92

2.57 1.93, 3.43 0.028

2.38, 3.57 <10-21

<10-10

<10-18

1.60, 2.43 <10-8

<10-5

<10-9

1.62, 2.53 <10-9

<10-4

<10-7

1.56, 2.81 <10-5

<10-3

<10-5

1.43, 4.55 0.0017

0.035

0.051

TURP conservatively managed

TURP conservatively managed PSA, dx Gleason

TURP

Rad prostatectomy 1

Rad prostatectomy 1 PSA, path Gleason, pT stage, surgical margin status

PSA, dx Gleason, percente positive cores

PSA, path Gleason (<7, 3+4, 4+3, >7), age at diagnosis, year of treatment, ECE, SVI, LNI, and surgical margin status

Radical Prostatectomy

Rad prostatectomy 2

Rad prostatectomy 2

Radical Prostatectomy

External beam Xrt

External beam Xrt

Needle Biopsy

Needle biopsy conservatively managed

Needle biopsy conservatively managed PSA, dx Gleason

Needle biopsy 2.02

1.65 1.31, 2.09 0.0022

2.55

2.09 1.05, 4.18 0.20

1.97

1.74 1.39, 2.17 0.015

2.10

1.97 1.41, 2.76 0.10

† PSA transformed to In (1 + PSA ng/mL); Gleason treated as 3-level factor (<7, 7, >7) unless otherwise noted; pTstage as integers for substages; age in years as continuous; year of treatment as integers, extracapsular extension (ECE), SVI (seminal vesicle involvement), lymph node involvement (LNI), and surgical margin status as binary; percent positive cores as continuous over interval (0,1).

* All coefficients are significant at 0.05 level.† Diagnostic for biopsy samples; pathologic for surgery tumor samples; treated as mintegers (1 for <7, 2 for 7, and 3 for >7).‡ In (1 + PSA ng/mL).

Study Title Prolaris vs Gleason Score† Prolaris vs PSA‡

0.57 0.27TURP conservatively managed

Rad prostatectomy 1

Rad prostatectomy 2

External beam Xrt

Needle biopsy conservatively managed 0.37 0.14

0.23 0.31

0.22 0.21

0.18 0.11

Even

t-Fr

ee S

urvi

val

Perc

ent o

f Coh

ort

Years

Prolaris Score

1

0.9

0.8

0.7

0.6

0.5

30

25

20

15

10

5

0

0

-1.5to-1

0.5to1

2.5to 3

4to4.5

-0.5to0

1.5to2

3.5to 4

5to5.5

-2to

-1.5

0to0.5

2to2.5

-1to

-0.5

1to1.5

3to3.5

4.5to5

2 4 6 8 10

TURP

NEEDLE BIOPSY

RP1

RP2

EXTERNAL BEAM XRT

TURP

NEEDLE BIOPSY

RP1

RP2

EXTERNAL BEAM XRT

Testing for Prostate Cancer Agressiveness

clinical summary

Background:• Prostate cancer has a highly variable natural history and accurately assessing the tumor’s

aggressiveness based on clinical and pathologic features is challenging.

• Novel prognostic markers are needed to more precisely guide therapeutic decisions.

• The Prolaris® test measures the activity of cell cycle progression genes in prostate cancer tissue.

• Prolaris has been tested in five distinct cohorts.

Methods: • All studies were retrospective.

• Formalin fixed prostate tissue from men with adenocarcinoma were analyzed.

• The Prolaris score® is calculated by measuring the average RNA expression of 31 cell cycle progression

genes normalized by the average expression of 15 housekeeping genes as quantitated by RT-PCR.

Summary of Prostate Cancer Studies

* Censored at 5 years.

Myriad, the Myriad logo, Prolaris and the Prolaris logo are either trademarks or registered trademarks of Myriad Genetics, Inc., in the United States and other jurisdictions. ©2013, Myriad Genetics GmbH. Not for distribution in USA.

Prolaris®: a novel genetic test for prostate cancer prognosis

Myriad Genetics GmbHLeutschenbachstrasse 958050 ZurichSwitzerland

www.myriad.com

Conclusions:

• Prolaris predicts prostate cancer outcome in multiple patient cohorts and in diverse clinical settings.

• Prolaris provides independent information beyond clinicopathologic variables.

• Prolaris helps to further differentiate aggressive prostate cancer from indolent cancer.

PRO

L/PS

TR/C

UZI

CK/

07/1

3/EN

V1

A prognostic medicine product for prostate cancer.Prolaris® testing assesses prostate cancer aggressiveness in conjunction with other clinical parameters. Prolaris® measures the expression level of genes involved with cell cycle progression (CCP) in tumor specimens to predict disease outcome.

For more information please contact your local Myriad Representative.

Poster presented at the Global Congress on Prostate Cancer 2013

Prolaris®: a novel genetic test for prostate cancer prognosis

Jack Cuzick1, Matthew Cooperberg2, Greg Swanson3, Stephen Freedland4, Julia Reid5, Gabrielle Fisher1, Jerry Lanchbury5, Alexander Gutin5, Marcello Paglione5, Steven Stone5,

Peter Carroll2, Michael Brawer5, and on behalf of the Transatlantic Prostate Group

1. Center for Cancer Prevention, Wolfson Institute of Preventive Medicine, London, UK 2. Department of Urology, UCSF Hellen Diller Family Comprehensive Cancer Center, San Francisco, CA

3. Departments of Radiation Oncology, Urology and Radiology, University of Texas Health Science Center San Antonio, San Antonio, TX 4. Department of Surgery, Durham VA Medical Center and Department of Surgery, Duke University School of Medicine, Durham, NC

5. Myriad Genetics, Inc. , Salt Lake City, UT

Study Title Sample Type Number of Patients (events)

Event Reference

Biopsy 337 (76) death from prostate cancer Cuzick et al. Lancet Oncology 2011;12(3):245-55.

Cuzick et al. Lancet Oncology 2011;12(3):245-55.

Cooperberg et al. Journal of Clinical Oncology 2013;31:1428-34.

Freedland et al. 2013; In Press.

Cuzick et al. British Journal of Cancer 2012;106:1095-99.

biochemical recurrence

death from prostate cancer

biochemical recurrence

biochemical recurrence*

353 (132)

349 (90)

413 (83)

141 (19)

TURP conservatively managed

Rad prostatectomy 1

Rad prostatectomy 2

External beam Xrt

Needle biopsy conservatively managed

Biopsy

Biopsy

Surgical tumor

Surgical tumor

Results:• Prolaris was a highly significant predictor of outcome in all five studies.

• Prolaris was the dominant predictor in all but one of the studies in multivariate analysis.

• In all five studies, the hazard ratios (HRs) per unit of change in the Prolaris score were remarkably

similar, ranging from 1.97 to 2.92.

• These HRs indicate that the effect size for the Prolaris score is robust in varying clinical settings.