On the Road to Personalized Cancer Treatments

CAGPO October 21, 2012Calgary

Lucile Robillard MDGPO Ottawa Hospital Cancer Centre

Breast CancerBreast Cancer

First cancer to benefit from prognostic and Markers• ER

PR• PR• Her 2

Prognostic marker offers information on survival

Predictive marker offers relative benefit of a therapy

Breast CancerBreast Cancer

• Tamoxifen has been the backbone ofTamoxifen has been the backbone of adjuvant therapy in node positive postmenopausal women since the early p p y1980’s

• The discovery of the Her-2 antibody y yhelped explain why patients with overall similar pathological and clinical

t ti i d i dpresentations experienced varied recurrence patterns

Breast CancerBreast Cancer

Oncotype Dx for early stage breast CaOncotype Dx for early stage breast Ca• 21 gene assay

ER/PR H 2 d Ki67 di ti• ER/PR, Her-2 and Ki67 are predictive on their own

• The above are important components of the assay

• Oncotype Dx for breast ca determines a Recurrence Score

• The RS results assess the likelihood of distant recurrence and chemotherapy benefit

• The RS is both prognostic and predictive• In node –ve and ER +ve disease it adds

information leading to therapy changes in 37% ofinformation leading to therapy changes in 37% of patients

• 4% of patients received CT+HT rather than HT alonealone

• 33% received HT alone rather than CT+HT based on the result

• Potentially reducing harm

Colon Cancer

In colon cancer the first marker leading a

Colon Cancer

In colon cancer the first marker leading a therapeutic decision was the discovery of the imprtnce K ras gene in colon cancerthe imprtnce K ras gene in colon cancer

Th CO 17 t i l h d ll b fit fThe CO-17 trial showed a small benefit of Bevcizumab in metastatic colon cancer

ti t h h f il d t t t ith TSpatients who has failed treatment with TS inhibitors, oxaliplatin and irinotecan

Colon CancerColon Cancer• Subsequent analysis if the tumor tissue 0f the CO-q y

17 patients demonstated the almost total lack of response to egfr RX on patients with Mutated K ras geneg

• 40% of patients have the mutation and were previously receiving a therapy for which there was no chance of benefittingno chance of benefitting

• Less potential toxicity• Earlier assessment for Phase 1 clinical trials for

ti t b i f ll d i t d i thi tpatients being followed in centres doing this type of research

Colon Cancer-Adjuvant SettingColon Cancer Adjuvant Setting

15% of colorectal cancers are characterized15% of colorectal cancers are characterized by deficient DNA mismatch repair (MMR) leading to microsatellite instability (MSI) andleading to microsatellite instability (MSI) and mutations in critical genes involved in carcinogenesiscarcinogenesis.

MMR d fi i t MSI Hi h MSI itiMMR-deficient= MSI-High= MSI positive

Mismatch Repair Deficiency (MMR‐D):U i Bi l i l S b f C l CUnique Biological Subgroup of Colon Cancer 

IHC for MMR protein status

MLH1+ MSH2‐

MSH2+MLH1‐

PCR on tumor DNA for MSI ( i lli

Thus, IHC for MMR proteins and PCR for MSI detect two manifestations of the same tumor biology:

Imai and Yamamoto. Carcinogenesis 2008Umetani,  Annals of Surgical Oncology 2000Rosen et al.  Modern Pathology (2006) 19, 1414‐1420

(microsatellite instability)•MMR‐D is synonymous with MSI‐H

•MMR‐P is synonymous with MSI‐L/MSS

Colon Cancer-Adjuvant SettingColon Cancer Adjuvant Setting

Analysis of tumors from large randomizedAnalysis of tumors from large randomized trials has shown that MMR-D status is prognostic for both stage 2 and 3 patientsprognostic for both stage 2 and 3 patients. These patients have a low recurrence risk.

In stage 2 disease MMR-D is predictive of a l k b fit f FU d LV ( ibllack benefit from FU and LV (possibly a negative impact)

MMR‐D Identifies Resected Colon Cancer P i Wi h L R Ri kPatients With Low Recurrence Risk

No adjuvant chemotherapy n=287

MMR-D

MMR-P

• Multiple studies have consistently demonstrated that the ~15% patients with MMR‐D have markedly lower recurrence risk than the average stage II colon cancer patient

Ribic 2003 NEJM 349:247 

stage II colon cancer patient• MMR not yet a standardized marker in clinical practice

MMR‐D and Disease Free Survival in Stage II Colon C U ili f Adj 5FU ThCancer: Utility of Adjuvant 5FU Therapy

Sargent 2010 JCO 28:3219

Whether 5FU is harmful in MMR-D patients remains controversial, but at best, 5FU appears to yield little, if any, benefit for MMR-D patients

Oncotype DX® Colon Cancer AssayOncotype DX Colon Cancer Assay

Personalizing Risk Assessment in the Management of Stage II and III Colon

CCancer

Current Management of S II C l CStage II Colon Cancer

• NCCN Guidelines™ list wide range of “acceptable”g pmanagement strategies for resected stage II colon cancer:1– ObservationObservation– 5FU/LV or capecitabine– 5FU/LV/oxaliplatin (for high-risk features)

Cli i l t i l– Clinical trial• Estimated % receiving adjuvant therapy: 25-35%

– Use of adjuvant regimens in practice today:2j g p y• 5FU/LV 3%• FOLFOX + Avastin 5%• FOLFOX 89%

1. NCCN® Clinical Practice Guidelines for Oncology: Colon Cancer v2.2011. National Comprehensive Cancer Network (NCCN) and NCCN areregistered trademarks of NCCN.  NCCN do not endorse any product or therapy

2. OncoReport: Medical Oncology T3 2010, Interactive Clinical Intelligence, www.icimrr.com 

Diapositive 14

KB1 NCCN trademarks info / update market research numbersKristin Baehner; 2011-08-11

Existing Tools for Selecting Stage II P ti t f T t t A I d tPatients for Treatment Are InadequateRecurrence Risk Treatment Benefit• Bowel obstruction or perforation• T‐Stage• # of nodes assessed• Tumor grade

• MMR?

Tumor grade• Lymphatic/vascular invasion• Margin status• MMR

According to current guidelines:1,2• No molecular markers have been routinely established in clinical practice for stage II colon cancer.

• Treatment decisions are based on the expectation that higher risk stage II patients derive larger absolute benefit with adjuvant chemotherapy.

1. NCCN® Clinical Practice Guidelines for Oncology: Colon Cancer v2.2011.2. Benson AB 3rd, et al. J Clin Oncol. 2004;22:3408‐3419.

The Clinical Question in Stage II Colon Cancer: Which Patients Should Receive Adjuvant Chemotherapy?Should Receive Adjuvant Chemotherapy?

• It is unclear which 75-80% of patients are cured with psurgery alone

• Absolute chemotherapy benefit is small • Chemo has significant toxicity and impacts quality of life

– Median age 71 years old; comorbidities and competing causes of mortalityof mortality

• Selection of patients for chemotherapy is subjectively based on– Risk assessment with a limited set of clinical/pathologic markers– Patient age, comorbidities, patient preference

The 12-Gene Oncotype DX® Colon Cancer R S ® R ltRecurrence Score® Result

Recurrence Score Genes and Algorithm

CELL CYCLECELL CYCLEKiKi--6767 REFERENCEREFERENCE

STROMALSTROMALFAPFAP

CC--MYCMYCMYBL2MYBL2

REFERENCEREFERENCEATP5EATP5EGPX1GPX1PGK1PGK1UBBUBB

INHBAINHBABGNBGN

UBBUBBVDAC2VDAC2

GADD45BGADD45BGADD45BGADD45B

Recurrence Score =Recurrence Score = 0.15 x Stromal Group0.15 x Stromal Group0 30 C ll C l G0 30 C ll C l G-- 0.30 x Cell Cycle Group0.30 x Cell Cycle Group

+ 0.15 x GADD45B + 0.15 x GADD45B

Development and Validation of the Oncotype DX® Colon Cancer Assay for Use in Stage II/III Colon Cancer

Development Studies (Surgery) Development Studies (5FU/LV)

Colon Cancer Technical Feasibility

Development Studies (Surgery)NSABP C-01/C-02 (n = 270)

Cleveland Clinic (n = 765)

Development Studies (5FU/LV)NSABP C-04 (n = 308)NSABP C-06 (n = 508)

Standardization and Validation of Analytical Methods

Selection of Final Gene List & Algorithm

Clinical Validation Study – Stage II Colon CancerQUASAR (N = 1436)

Confirmation Study – Stage II Colon Cancer CALGB 9581 (N = 690)

Clinical Validation Study – Stage II/III Colon Cancer5FU vs 5FU+Oxaliplatin NSABP C-07 (N = 892)

Publication: QUASAR Validation Study for the O t DX® A i St II C l COncotype DX® Assay in Stage II Colon Cancer

Gray et al. J Clin Oncol. 2011.

QUASAR Results: Colon Cancer Recurrence Score®

R lt P di t R F ll i SResult Predicts Recurrence Following Surgery

Prospectively-defined Primary Analysis in Stage II Colon Cancer (n = 711)

s 30%

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Recurrence Score Result0 10 20 30 40 50 60 70

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Kerr et al. ASCO 2009. Abstract 4000.Gray et al. J Clin Oncol. 2011.

QUASAR Results: Clinical/Pathological CovariatesClinical/Pathological Covariates

and RecurrencePre-specified Multivariate Analysis, Surgery Alone Patients (n = 605)

Variable Categories HR 95% CI P value

Recurrence Score® Continuous per 25 units 1.61 (1.13, 2.29) 0.008

Mi t h R i 13% d fi i t 87% fi i t 0 32 (0 15 0 69) <0 001Mismatch Repair 13% deficient vs 87% proficient 0.32 (0.15, 0.69) <0.001

T stage 15% T4 vs 85% T3 1.83 (1.23, 2.75) 0.005

Tumor grade 29% high vs 71% low 0.62 (0.40, 0.96) 0.026

# of nodes examined 62% <12 vs 38% ≥ 12 1.47 (1.01, 2.14) 0.040

LVI 13% present vs 87% absent 1.40 (0.88, 2.23) 0.175

In these multivariate analyses, the Recurrence Score result, MMR status, and T-stage were found to be the most significant , g g

independent predictors of recurrence risk.

Kerr et al. ASCO 2009. Abstract 4000.Gray et al. J Clin Oncol. 2011.

QUASAR Results: Recurrence Score® Result, T-Stage, and MMR Deficiency Are Key Independent Predictors

f S C C

45%

of Recurrence in Stage II Colon Cancer

30%

35%

40%

45%

T4 and MMR proficient (13%)

t 3 Y

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20%

25%

30%

T3 and MMR proficient (74%)

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0 10 20 30 40 50 60 70

Rare patients (2% of all patients) with T4 MMRRare patients (2% of all patients) with T4 MMR D tumors had estimatedD tumors had estimated

R

Recurrence ScoreRare patients (2% of all patients) with T4, MMRRare patients (2% of all patients) with T4, MMR--D tumors had estimated D tumors had estimated

recurrence risks that approximated (with large confidence intervals) those for recurrence risks that approximated (with large confidence intervals) those for patients with T3 stage, MMRpatients with T3 stage, MMR--P tumors and were not included in this figure.P tumors and were not included in this figure.

Kerr et al. ASCO 2009. Abstract 4000.

Estimated Absolute Benefits from 5FU Increase with Increasing Recurrence Score based on Similar Proportional Benefits Across p

Recurrence Score® Groups in QUASAR

L R S I t di t R Hi h R SLow Recurrence Score group (<30)

Intermediate Recurrence Score group (30-40)

High Recurrence Score group (≥41)

Proportional reductions in risk of recurrence with 5FU chemotherapy Proportional reductions in risk of recurrence with 5FU chemotherapy were similar across Recurrence Score groups. were similar across Recurrence Score groups. Therefore, absolute benefit with adjuvant 5FU treatment increases with Therefore, absolute benefit with adjuvant 5FU treatment increases with increasing Recurrence Score values.increasing Recurrence Score values.

Gray et al. J Clin Oncol 2011.

Validation of a 12-Gene Colon Cancer Recurrence Score® in Stage II Colon Cancer

Patients From CALGB 9581

AP Venook,1 D Niedzwiecki,2 M Lopatin,3 M Lee,3 PN Friedman,4W Frankel,5 K Clark-Langone,3 C Yoshizawa,3 C Millward,3 S Shak,3W Frankel, K Clark Langone, C Yoshizawa, C Millward, S Shak,

RM Goldberg,6 NN Mahmoud,7 RL Schilsky,4 MM Bertagnolli8

1. University of California, San Francisco, CA; 2. Duke University, Durham, NC; y , , ; y, , ;3. Genomic Health, Redwood City, CA; 4. The University of Chicago, IL;

5. The Ohio State University, Columbus, OH; 6. University of North Carolina at Chapel Hill, NC; 7. University of Pennsylvania, Philadelphia, PA; 8. Brigham and Women's Hospital, Boston, MA

Venook et al. ASCO 2011. Abstract 3518.

CALGB 9581: Unique Opportunity to StudyL Ri k St II C l CLow Risk Stage II Colon Cancer

CharacteristicCharacteristic CALGB 9581CALGB 9581 QUASARQUASARRecurrence risk (5 yr) 14.6% 21.7%T4 6% 15%MMR D 22% 14%MMR-D 22% 14%Age ≥70 yrs 35% 20%<12 Nodes examined 47% 62%LVI 11% 14%High tumor grade 32% 31%

Compared to QUASAR, the CALGB 9581 population had:Compared to QUASAR, the CALGB 9581 population had:•• More patients aged More patients aged ≥70 years70 years•• Fewer patients with T4 tumorsFewer patients with T4 tumorspp•• More patients with MMRMore patients with MMR--deficiencydeficiency•• Overall lower recurrence risksOverall lower recurrence risks

Venook et al. ASCO 2011. Abstract 3518.

CALGB 9581 Primary Analysis: Association of Continuous Recurrence Score® Result With Recurrence RiskRecurrence Score® Result With Recurrence Risk

VariableVariable HRHR 95%95% CICI p Valuep Value

RS per 25 units 1.52 (1.09, 2.12) 0.013

• The continuous Recurrence Score value was significantly

fassociated with the risk of recurrence

• Strength of associationStrength of association consistent with QUASAR

Venook et al. ASCO 2011. Abstract 3518.

RS, Recurrence Score

Contribution of Recurrence Score® Result to Prediction of Recurrence Risk Beyond Clinical and Pathologic CovariatesRecurrence Risk Beyond Clinical and Pathologic Covariates

Pre-specified multivariable Cox regression of Recurrence Score result

HR

p gand covariates on RFI (n=656, 95% of all patients)

Variable HR 95% CI P valueRecurrence Score result per 25 Units 1.68 (1.18, 2.38) 0.004

T Stage (T4 vs T3) 0.93 (0.44, 1.97) 0.85T Stage (T4 vs T3) 0.93 (0.44, 1.97) 0.85

MMR Status (deficient vs proficient) 0.70 (0.42, 1.17) 0.17

Number of Nodes Examined (<12 vs ≥12) 1.14 (0.81, 1.60) 0.46

Tumor Grade (high vs low) 0.78 (0.51, 1.18) 0.24

LVI (present vs not) 1.39 (0.85, 2.26) 0.19

RFI, recurrence-free interval

Venook et al. ASCO 2011. Abstract 3518.

Development and Validation of the Oncotype DX® Colon Cancer Assay for Use in Stage II/III Colon Cancer

Development Studies (Surgery) Development Studies (5FU/LV)

Colon Cancer Technical Feasibility

Development Studies (Surgery)NSABP C-01/C-02 (n = 270)

Cleveland Clinic (n = 765)

Development Studies (5FU/LV)NSABP C-04 (n = 308)NSABP C-06 (n = 508)

Standardization and Validation of Analytical Methods

Selection of Final Gene List & Algorithm

Clinical Validation Study – Stage II Colon CancerQUASAR (N = 1436)

Confirmation Study – Stage II Colon Cancer CALGB 9581 (N = 690)

Clinical Validation Study – Stage II/III Colon Cancer5FU vs 5FU+Oxaliplatin NSABP C-07 (N = 892)

Validation of the 12-gene Colon Cancer Recurrence Score®

Result in NSABP C-07 as a Predictor of Recurrence in StageResult in NSABP C 07 as a Predictor of Recurrence in Stage II and III Colon Cancer Patients Treated with 5FU/LV (5FU)

and 5FU/LV + Oxaliplatin (5FU+Ox)

O’Connell MJ,1 Lee M,2 Lopatin M,2 Yothers G,1 Clark-Langone K,2 Millward C,2 Paik S,1 Sharif S,1 Shak S,2 Wolmark N1

1National Surgical Adjuvant Breast and Bowel Project, Pittsburgh, PA; 2Genomic Health, Inc., Redwood City, CA

O’Connell et al. ASCO 2012. Abstract 3512.

The Clinical Question in Stage III Colon Cancer: Which Patients Should Receive Oxaliplatin?Which Patients Should Receive Oxaliplatin?

• For patients with stage III colon cancer, current practice guidelines1

recommend 5-FU/LV + oxaliplatin for adjuvant therapy, and in the US, a growing majority of stage II colon cancer patients receive this regimen.2

H li l ti lik l b fit l f ti f t t d ti t (6− However, oxaliplatin likely benefits only a fraction of treated patients (6-7%)3,4 and comes with significant toxicity, including the prospect of long-term peripheral neuropathy.3-7

• Conventional clinical and pathologic risk factors do not adequately discriminate risk and expected absolute benefit of oxaliplatin to guide d i i kidecision-making.

1. NCCN Colon Cancer 2012 2. Abrams et al. J Clin Oncol. 2011. 3. Kuebler et al. J Clin Oncol. 2007. 4. Yothers et al. J Clin Oncol. 2011. 5. Andre et al. J Clin Oncol. 2009. 6. Land et al. J Clin Oncol. 2011. 7. Kuebler et al. Cancer. 2007.

NSABP C-07: A Key US Trial That Established Efficacy of Addition of Oxaliplatin to 5FU-based Adjuvant

• Phase III intergroup study1

Chemotherapy in Resected Colon Cancer

– Randomization: 5FU vs 5FU+oxaliplatin (FLOX)– 2,409 evaluable patients enrolled between 2000 and 2002

Prospectively collected tissue samples– Prospectively collected tissue samples– In combination with the MOSAIC study, established benefit of addingadding

oxaliplatin oxaliplatin to to 5FU 5FU in in adjuvant therapy adjuvant therapy of of colon cancercolon cancer

O’Connell et al. ASCO 2012. Abstract 3512. 1. Kuebler et al. J Clin Oncol. 2007.

Study ObjectivesStudy Objectives

Prospectively-designed study using archived tissue with pre-specified endpoints analytical methods and analysis plan (a “Prospectiveendpoints, analytical methods and analysis plan (a Prospective-Retrospective” study1)

P i Obj ti• Primary Objective:− Determine whether there is a significant relationship between the

continuous 12-gene Recurrence Score® value and recurrence risk i t II/III ti t t t d ith 5FU 5FU+ li l tiin stage II/III patients treated with 5FU or 5FU+oxaliplatin

• Secondary Objectives− Determine whether the Recurrence Score result provides

significant information beyond number of nodes examined, pathologic T-stage, tumor grade and MMR status

− Compare recurrence risk between high and low Recurrence Score groups defined using pre-specified cut-points

O’Connell et al. ASCO 2012. Abstract 3512. 1. Simon et al. J Natl Cancer Inst. 2009.

Study Population

Parent C-07 studyn=2,409

Eligible patients with available tumor tissuen=1,860 (77%)

Randomly selected 50% of patients with available tissuewith stratification on recurrence status and stage

Study Cohort (n=929)

37 excluded (4%):9 insufficient tissue

19 ineligible histology9 RNA quality/quantity

Final evaluable population (n=892)

O’Connell et al. ASCO 2012. Abstract 3512.

Demographics and Clinical CharacteristicsDemographics and Clinical Characteristics

• Median follow up 8.6 years; 865 (97%) of 892 evaluable patients had complete follow-up at 3 years and 840 (94%) had complete follow-up at 5 years.

• Recurrences− 31 (12%) of 264 stage II patients − 214 (34%) of 628 stage III patients214 (34%) of 628 stage III patients

O’Connell et al. ASCO 2012. Abstract 3512.

Pre-Specified Primary Analysis:Recurrence Score® Result Predicts Recurrence Risk in Stage II &

III Colon Cancer Patients in NSABP C-07 (n=892)

Variable Value HR HR 95% CI p-value

Stage <0.001g(by nodal status) Stage III A/B vs II 2.53 (1.70,3.78)

Stage III C vs II 5.29 (3.54,7.90)Treatment 5FU+Ox vs 5FU 0 76 (0 59 0 98) 0 033Treatment 5FU+Ox vs 5FU 0.76 (0.59,0.98) 0.033Recurrence Score result per 25 units 1.96 (1.50,2.55) <0.001

• Continuous Recurrence Score result is significantly associated with risk of recurrence controlling for effects of treatment and stage (by nodal status)− Interaction of Recurrence Score result and nodal status, treatment, and age

t i ifi t ( 0 90 0 48 d 0 76 ti l )were not significant (p=0.90, 0.48, and 0.76, respectively)

O’Connell et al. ASCO 2012. Abstract 3512.

Primary Analysis: Recurrence Score® Result Predicts Recurrence Risk in Stage II & III Colon Cancer Patients in NSABP C-07 (n=892)in Stage II & III Colon Cancer Patients in NSABP C 07 (n 892)

S lid 5FU St III CSolid: 5FU    Dashed: 5FU+Ox

Stage III Cp<0.001

Stage III A/B

Stage II

Solid: 5FUDashed: 5FU+Ox

O’Connell, et al. ASCO 2012. Abstract 3512.

Contribution of Recurrence Score® Result Beyond Clinical and Pathologic Covariates

P ifi d M lti i t A l i ( 892)Pre-specified Multivariate Analysis (n=892)

Variable Value HR HR 95% CI P value

Stage <0.001(by nodal status) Stage III A/B vs II 0.97 (0.55,1.71)

Stage III C vs II 2 07 (1 16 3 68)Stage III C vs II 2.07 (1.16,3.68)Treatment 5FU+Ox vs 5FU 0.82 (0.64,1.06) 0.12MMR MMR-D vs MMR-P 0.27 (0.12,0.62) <0.001T-stage T4 st II & T3-T4 st III vs

T3 st II & T1-T2 st III3.04 (1.84,5.02) <0.001

Nodes examined <12 vs ≥12 1 51 (1 17 1 95) 0 002Nodes examined 12 vs ≥12 1.51 (1.17,1.95) 0.002Tumor grade High vs Low 1.36 (1.02,1.82) 0.041Recurrence Score result per 25 units 1.57 (1.19, 2.08) 0.001

O’Connell et al. ASCO 2012. Abstract 3512.

R S ® R lt d Alt ti E d i tRecurrence Score® Result and Alternative Endpoints

Variable HR HR 95% CI P value

RS 25 it 1 60 (1 28 1 99) <0 001

Disease Free RS per 25 units 1.60 (1.28,1.99) <0.001Free Survival

Overall Survival

Variable HR HR 95% CI P valueSurvival

RS per 25 units 1.89 (1.46,2.44) <0.001

O’Connell et al. ASCO 2012. Abstract 3512.

ConclusionsConclusions

• As in stage II colon cancer, incorporating the Recurrence Score result into th li i l t t id dj t th d i i f t i ti tthe clinical context can guide adjuvant therapy decisions for certain patients with stage III colon cancer.− In particular, for certain stage IIIA/B patients, the finding of low

Recurrence Score disease (Recurrence Score result < 30) and thusRecurrence Score disease (Recurrence Score result < 30), and thus low recurrence risk and low absolute oxaliplatin benefit, may not justify the risk of potential toxicity from adding oxaliplatin.

• Analysis of new genes as potential predictors of oxaliplatin sensitivity and resistance is in progress.

• Risk stratification through anatomic staging, the Recurrence Score result and potentially other factors may enable clinical trial designs targeted to more homogeneous, well-defined low- and high-risk patient populations in the adjuvant settingthe adjuvant setting.

O’Connell et al. ASCO 2012. Abstract 3512.

Oncotype DX® Colon Cancer Assay Incorporating the Recurrence Score® Result into Treatment

• The Recurrence Score result predicts recurrence risk in stage II

Incorporating the Recurrence Score Result into Treatment

and III colon cancer, revealing underlying biology to provide value beyond conventional measures.

• The Recurrence Score result enables better discrimination of absolute treatment benefit as a function of risk, with greatest clinical utility in T3 MMR-P stage II and stage IIIA/B patients.

• Incorporating the Recurrence Score result into the context of clinicopathologic variables may b tt i f dj t thbetter inform adjuvant therapy decisions for patients with stage II and III colon cancer.

Oncotype Dx Colon cancer AssayOncotype Dx Colon cancer Assay

• Clinical Assay and Recurrence ScoreClinical Assay and Recurrence Score Evaluation Survey (CARES) Program

• Genomics Health has provided the OHCC• Genomics Health has provided the OHCC with 25 free kits to use at the discretion of the GI groupthe GI group

• The group has decided on clinical criteria f th f th kitfor the use of the kits

• Only stage 2 patients (no stage 3)

Criteria for use (cont’)Criteria for use (cont )

• Exclude T4 patientsExclude T4 patients• Exclude inadequate sampling(<12 nodes)

E l d t l• Exclude rectal• No signs on pathology for MSI (Right

sided lesion, lymphocytic infiltration, large mucinous component, poorly differentiated) unless tests are negative for MSI by IHC

Criteria(cont’)Criteria(cont )

• Patient fit and willing to takePatient fit and willing to take chemotherapy

• <9 weeks from surgery (gives time to get• <9 weeks from surgery (gives time to get the assay completed)P ti t l d itt d t• Patient already committed to chemotherapy regardless of result of O t DXOncotype DX