Gleason Score. Oncotype DX GPS. identified for. about surveillance. time to get sophisticated

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1 patient: MARK SMITH PSA 6.2 Gleason Score 6 Oncotype DX GPS 8 identified for active surveillance time to get sophisticated about surveillance

2 Accurate prediction of prostate cancer risk is needed at the time of biopsy Existing risk-assessment tools do not accurately and consistently identify which patients can be safely followed with Active Surveillance and who needs immediate treatment. Despite only a 3% chance of low-risk disease progressing and becoming life threatening, 9 out of 10 low-risk patients receive immediate treatment rather than Active Surveillance. 1,2 3% 97% 9/10: immediate treatment 1/10: Active Surveillance patient: MARK SMITH PSA 6.2 Gleason Score 6 Does Mark really have low-risk disease? 2

3 Sophisticated risk assessment lies in the tumor biology The Oncotype DX Prostate Cancer Assay analyzes complex individual tumors to provide information beyond traditional risk-assessment tools. This biopsy-based genomic assay: Has been developed and validated in 7 studies in over 1100 patients Is highly predictive of adverse pathology defined as either high grade or non-organ-confined disease Addresses the critical issues of heterogeneity and undersampling Generates a Genomic Prostate Score (GPS) which reveals the biology and behavior of newly diagnosed prostate cancers GPS is a quantitative result, ranging from 0-100, that represents the biologic aggressiveness of the individual tumor Multiple studies show that most patients with low-grade, organconfined disease can be successfully and safely managed with ACTIVE SURVEILLANCE. In seven Active Surveillance studies looking at over 3700 patients, the cancer-specific survival rate was 99.4% with follow-up up to 82 months. 3 The Oncotype DX Prostate Cancer Assay provides more information and more precision beyond the standard clinical criteria, which in turn gives you more confidence in your treatment decisions for early-stage prostate cancer. Peter Carroll, MD, MPH Chair, UCSF Department of Urology 3

4 GPS development: A proven and rigorous approach The Oncotype DX Prostate Cancer Assay was developed on the basis of two collaborative development studies with the Cleveland Clinic to specifically address the many challenges inherent in prostate cancer risk assessment. Optimized a technology platform to reliably analyze small amounts of tissue obtained from biopsy Demonstrated consistent results in both prostatectomy and biopsy studies to overcome tumor heterogeneity and undersampling Identified a final set of 17 genes across 4 key biological pathways predictive of high-grade and/or non-organ-confined disease GENES GENE IDENTIFICATION STUDY Associated gene expression levels with clinical recurrence in both the dominant and highest Gleason pattern tumors. Selected genes are robust to tumor heterogeneity and predictive of clinical and biochemical reccurence GENE REFINEMENT STUDY Tested in needle biopsies, confirmed as predictive of aggressive prostate cancer pathology ASSAY FINALIZATION AND ANALYTICAL VALIDATION Finalized and validated the precision and reproducibility of the GPS algorithm 4

5 Incorporating multiple genomic pathways important in prostate cancer The combination of multiple pathways is more predictive than any single pathway Androgen Signaling AZGP1 FAM13C KLK2 SRD5A2 Stromal Response BGN COL1A1 SFRP4 Proliferation TPX2 Cellular Organization FLNC GSN GSTM2 TPM2 Reference ARF1 ATP5E CLTC GPS1 PGK1 GPS algorithm + Stromal Response Group - Cellular organization group - androgen signaling group + proliferation GROUP each gene is individually weighted in the final algorithm The clinical challenge that we were able to address was capturing the underlying biology of each patient s prostate cancer, predictive of clinically aggressive disease, from a needle biopsy regardless of whether the primary or highest Gleason pattern tumor was sampled. Eric Klein, MD Chairman, glickman urological and kidney institute, Cleveland Clinic Foundation 5

6 GPS validation: Prediction of aggressive prostate cancer from biopsy Genomic Health collaborated with the University of California, San Francisco (UCSF) to validate the Oncotype DX Prostate Cancer Assay in needle biopsies from patients diagnosed with very low- to low-intermediate* clinical risk according to the NCCN clinical risk criteria. Primary analysis shows strong predictive value: GPS was validated as a predictor of surgical grade and stage with a P value of Predictive power demonstrated in very low- to low-intermediate risk patients: Validated in 395 patients with very low- to low-intermediate* clinical risk tumors All patients were candidates for Active Surveillance based on their clinical risk profile Proven performance in needle biopsy samples: Performed on manually micro-dissected tumor tissue from a single needle biopsy block 96% of biopsies yielded successful GPS results 99.5% of samples with 10ng RNA yielded successful GPS results improves risk discrimination: Incorporation of GPS with conventional tools provides additional information to confidently choose between Active Surveillance and immediate treatment Contemporary patient population Clinical characteristics of patients Age at diagnosis Mean Range 58.3 years years Race Caucasian African American Other/unknown (91%) (3%) (6%) PSA Clinical T-Stage Central Biopsy Gleason Score 0-4 > 4-10 > T1c T2a T2b/c (21%) (66%) (13%) (58%) (30%) (12%) (76%) (24%) 6

7 Adding independent Predictive Information beyond conventional tools GPS per 20 units Prediction of high-grade disease Prediction of non-organ-confined disease Prediction of high-grade and/ or non-organ-confined disease Univariable Multivariable Odds Ratio P Value Odds Ratio P Value 2.48 < < < < Adjusted for NCCN clinical risk criteria*. Clinical and pathologic risk parameters in the validation study very low low low-intermediate* gleason Score 6 PSA < 10ng/mL Clinical stage T1c Fewer than 3 positive biopsy cores, 50% involvement in any core PSA density <.15ng/mL/g gleason Score 6 PSA < 10ng/mL Clinical stage T1-T2a gleason Score 6 AND Clinical stage T2b-T2c, OR PSA 10-20ng/mL OR gleason Score 3+4, AND all of the following: - Fewer than 4 positive biopsy cores - Clinical stage T1-T2c - PSA 20ng/mL *NCCN and NCCN Guidelines are trademarks of the National Comprehensive Cancer Network. NCCN does not endorse any therapy or product. 7

8 Adding precision by combining biologic and clinical risk NCCN Very Low-Risk Patient NCCN Low-Risk Patient NCCN Intermediate-Risk Patient Population-Based Clinical Risk Assessment Very Low Risk 10% (n=37) Low Risk 49% (n=191) Intermediate Risk 41% (n=160) GPS Individualized Biologic and Clinical Risk Assessment Very Low Risk 26% (n=100) Low Risk 31% (n=119) Intermediate Risk 44% (n=169) 100% 84% 56% 30% more favorable Likelihood of Favorable Pathology less favorable Patients highlighted are for illustrative purposes only. 7 patients were not included in analysis. The addition of GPS: 8 Expanded the very low-risk Active Surveillance population from 10% to 26% Predicted that 35% of men with NCCN low-risk disease had more favorable pathology consistent with very-low risk and 10% had less favorable pathology consistent with intermediate-risk disease Precisely identifies the patient s tumor biology within his risk category and replaces the population-based risk assessment with a truly personalized risk assessment

9 More precise risk discrimination delivers confident decision making Clinical Criteria Very low low intermediate Biologic Criteria GPS Actionable Information Very low low intermediate more favorable CONSISTENT WITH LESS favorable active surveillance immediate treatment GPS should be interpreted in the context of the patient s clinical risk assessment. On the Oncotype DX report, a NCCN low-risk patient will have 1 of the 3 scenarios provided below: More Favorable than clinical criteria alone: The biology of the tumor is predicted to be less aggressive, and the risk profile is predicted to be more favorable than NCCN low-risk disease. These patients may be appropriate for Active Surveillance. Consistent With clinical criteria: The biology of the tumor is predicted to be consistent with the risk profile of men with NCCN low-risk disease. These patients may be appropriate for either Active Surveillance or immediate treatment. Less Favorable than clinical criteria alone: The biology of the tumor is predicted to be more aggressive, and the risk profile is predicted to be less favorable than NCCN low-risk disease. These patients may be appropriate for immediate treatment. 9

10 Case Study: Mark Smith a typical low-risk patient patient: MARK SMITH PSA 6.2 Gleason Score 6 Oncotype DX GPS 8 identified for Active Surveillance With a GPS of 8, Mark s tumor is predicted to be less aggressive than NCCN low-risk disease Mark s risk assessment is MORE FAVORABLE than predicted by clinical criteria alone His likelihood of favorable pathology is substantially higher than would be predicted by clinical factors alone with this information, Mark and his urologist confidently chose Active Surveillance NCCN Clinical Risk Assessment Very low low intermediate GPS 8 GPS (Biologic) and NCCN (Clinical) Risk Assessment Very low more favorable low intermediate 100% 84% 30% more favorable Likelihood of Favorable Pathology less favorable 10

11 Patient report provides actionable risk information Incorporating GPS with clinical measures provides more accurate and precise assessment Likelihood of Favorable Pathology Favorable pathology is defined as freedom from high-grade (dominant pattern 4 or any pattern 5) and/or non-organ-confined (pt3) disease 84% Clinical criteria alone cannot precisely or accurately predict an individual s likelihood of favorable pathology (95% CI: 76%-89%) Freedom from High-Grade Disease (dominant Gleason pattern 4 or any pattern 5): 92% (95% CI: 86%-95%) Freedom from Non-Organ-Confined Disease (pathology T3 stage): 88% (95% CI: 82%-93%) Individual components of favorable pathology are separately reported as high-grade disease and non-organ-confined disease When GPS predicts pathology to be less favorable than expected by clinical criteria alone, the likelihood of high-grade disease and/or non-organ-confined disease may provide important additional information for treatment planning 11

12 A decade of expertise Genomic Health is dedicated to addressing the challenges of cancer treatment by utilizing genomics to help physicians and patients choose the most appropriate treatment options with confidence. Together, our precision genomic assays in breast and colon cancer have helped over 335,000 patients and their physicians more accurately chart their treatment course. Now, with the Oncotype DX Prostate Cancer Assay, that level of confidence is also available for the treatment of men with newly diagnosed prostate cancer Oncotype DX Assay for breast cancer Oncotype DX Assay for colon cancer Oncotype DX Assay for prostate cancer References: 1. Wilt TJ, Brawer MK, Jones KM, et al. Radical prostatectomy versus observation for localized prostate cancer. N Engl J Med. 2012;367(3): Cooperberg MR, Broering JM, Kantoff PW, et al. Contemporary trends in low risk prostate cancer: risk assessment and treatment. J Urol. 2007;178:S14-S Glass AS, Cooperberg MR, Meng MV, et al. Role of active surveillance in the management of localized prostate cancer. J Natl Cancer Inst Monogr. 2012;2012(45): Klein E. A genomic approach to Active Surveillance. Glickman Urological and Kidney Institute Research Notes. 2013;1:1,3,4. Genomic Health and Oncotype DX are registered trademarks of Genomic Health, Inc Genomic Health, Inc. All rights reserved. GHI40007_0513 Ordering the Oncotype DX Prostate Cancer Assay is simple, quick, and efficient. Visit OncotypeDX.com Call 877-ONCOTYPE ( ) Talk to your Regional Urogenomic Liaison