Transcript Document

Oncotype DX®
Breast Cancer Assay
Agenda
• Introduction
• Development of Oncotype DX®
• Clinical Studies
–
–
–
–
–
Validation studies
Hormonal therapy benefit study (NSABP B-14)
Chemotherapy benefit study (NSABP B-20)
Node + study (SWOG 8814)
Decision Impact Studies
• TAILORx
• Genomic Health Clinical Laboratory Experience
• Clinical Summary
2
Breast Cancer Treatment Planning:
History
• Treatment planning for N–, ER+ disease
is based on:
– Traditional prognostic factors with limited
predictive power (tumor size, patient age) or
poor reproducibility (tumor grade)
– IHC markers (eg, Ki-67) lacking
standardization and validation
– Limited insight into relative benefits of
chemotherapy for different individuals
Bundred. Cancer Treat Rev. 2001;27:137-142.
3
Breast Cancer Treatment Planning:
Not Optimized
• Chemotherapy treatment for N–, ER+
disease
– Many women are offered chemotherapy,
knowing that few benefit
– Prior to 2007, guidelines assumed all patients
benefit equally
– Some patients are under-treated, many others
are over-treated
4
What Would Your Treatment Strategy
Be For This Patient?
• Age: 61
• ER: 95%
• PR: 95%
• Tumor Type: IDC
• Tumor Size: 0.6 cm*
• Tumor Grade: 2
• HER-2 neu Neg (FISH)
*Additional 6 mm on re-excision
www.adjuvantonline.com. Standard version 8.0. Accessed 8/07
5
Recurrence Score: 36
Average Rate of Distant Recurrence at 10 Yrs: 25%
RESULTS
Recurrence Score =
36
CLINICAL EXPERIENCE
Patients with a Recurrence Score of 36 in clinical validation study had an Average Rate of Distance
Recurrence at 10 years of 25% (95% CI: 19%–30%)
6
Oncotype DX®:
Unmet Clinical Need for Better Markers
Optimize
High risk/
Large chemo benefit chemotherapy +
local therapy +
hormonal therapy
Biopsy
or
Resection
Robust
markers
Low risk/
Little chemo benefit
Optimize local
therapy and
hormonal
therapy
7
Development and Validation of a 21-Gene Assay
for N–, ER+, Tam+ Patients
YEAR
Develop real-time RT-PCR method for paraffin block
2001
Select candidate genes (250 genes)
2002
Model building studies
(N = 447, including 233 from NSABP B-20)
2002
Commit to a single 21-gene assay
2003
Validation studies in NSABP B-14 and
Kaiser Permanente
2003
Paik et al. N Engl J Med. 2004;351:2817-2826.
8
Oncotype DX® Technology:
Final Gene Set Selection
Objective
Gene expression and relapse-free interval correlations across three
independent studies – testing 250 genes in 447 patients
N
Node
Status
ER
Status
Treatment
NSABP B-20,
Pittsburgh, PA
233
N–
ER+
Tamoxifen (100%)
Rush
University,
Chicago, IL
78
>10
positive
nodes
ER+/–
Tamoxifen (54%)
Chemotherapy
(80%)
Providence
St. Joseph’s
Hospital,
Burbank, CA
136
N+/–
ER+/–
Tamoxifen (41%)
Chemotherapy
(39%)
Study Site
21 genes and
Recurrence
Score (RS)
algorithm
Paik et al. SABCS 2003. Abstract #16.
Cobleigh et al. Clin Cancer Res. 2005;11(24 Pt 1):8623-8631.
Esteban et al. Proc ASCO 2003. Abstract #3416.
9
Oncotype DX® 21-Gene
Recurrence Score (RS) Assay
16 Cancer and 5 Reference Genes From 3 Studies
PROLIFERATION
Ki-67
STK15
Survivin
Cyclin B1
MYBL2
ESTROGEN RS =
ER
PR
Bcl2
SCUBE2
GSTM1
INVASION
Stromelysin 3
Cathepsin L2
HER2
GRB7
HER2
BAG1
CD68
REFERENCE
Beta-actin
GAPDH
RPLPO
GUS
TFRC
+ 0.47 x HER2 Group Score
- 0.34 x ER Group Score
+ 1.04 x Proliferation Group Score
+ 0.10 x Invasion Group Score
+ 0.05 x CD68
- 0.08 x GSTM1
- 0.07 x BAG1
Category
RS (0 -100)
Low risk
RS <18
Int risk
RS 18 - 30
High risk
RS ≥ 31
Paik et al. N Engl J Med. 2004;351:2817-2826.
10
Oncotype DX® Clinical Validation:
RS as Continuous Predictor
40%
IntermediateRisk Group
Distant Recurrence at 10 Years
Low-Risk Group
35%
High-Risk Group
My RS is 30. What is the chance
of recurrence within 10 years?
30%
25%
20%
15%
10%
5%
95% CI
0%
0
5
10
15
20
25
30
35
40
45
50
Recurrence Score
11
Oncotype DX®
Clinical Validation:
The NSABP B-14 Study*
*Paik et al. N Engl J Med. 2004;351:2817-2826.
Oncotype DX® Clinical Validation:
Genomic Health – NSABP B-14
• Objective: Prospectively validate RS as predictor of
distant recurrence in N–, ER+ patients
• Design
Placebo—not eligible
Randomized
Tamoxifen—eligible
Registered
Tamoxifen—eligible
– Multicenter study with prespecified 21-gene assay,
algorithm, endpoints, analysis plan
Paik et al. N Engl J Med. 2004;351:2817-2826.
13
Oncotype DX® Clinical Validation:
B-14 Results – Distant Recurrence
Distant Recurrence Over Time – All 668 Patients
Proportion without Distant Recurrence
100%
90%
80%
70%
60%
Proportion Without
Distant Recurrence at
10 years = 85%
50%
40%
30%
20%
10%
0%
0
2
4
6
8
10
Years
12
14
16
Paik et al. N Engl J Med. 2004;351:2817-2826.
14
Oncotype DX® Clinical Validation:
B-14 Results – Distant Recurrence
Distant Recurrence for the three distinct cohorts identified
Proportion without Distant Recurrence
100%
90%
80%
70%
60%
50%
P <0.001
40%
30%
RS <18 n = 338
20%
RS 18-30 n = 149
10%
RS 31 n = 181
0%
0
2
4
6
8
Years
10
12
14
16
Paik et al. N Engl J Med. 2004;351:2817-2826.
15
Oncotype DX® Clinical Validation:
B-14 Results – Distant Recurrence
Risk Group
% of
10-yr Rate of
Patients Recurrence
95% CI
Low (RS <18)
51%
6.8%
4.0%, 9.6%
Intermediate (RS 18-30)
22%
14.3%
8.3%, 20.3%
High (RS ≥31)
27%
30.5%
23.6%, 37.4%
Test for the 10-year Distant Recurrence comparison between the
low-and high-risk groups: P <0.001
Paik et al. N Engl J Med. 2004;351:2817-2826.
16
Oncotype DX® Clinical Validation: B-14 Results
Multivariate Analysis Confirms Power of RS
Multivariate Cox Models: Age, Size + RS
Variable
Hazard Ratio
95% CI
P value
Age ≥50
0.71
(0.48, 1.05)
0.084
Size >2.0 cm
1.26
(0.86, 1.85)
0.231
Recurrence
Score
3.21
(2.23, 4.61)
<0.001
Age at surgery used as a binary factor: 0 = <50 yr, 1 = ≥50 yr.
Clinical tumor size (CTS) used as a binary factor: 0 = ≤2 cm, 1 = >2 cm.
Recurrence Score used as a continuous variable, with HR relative to an increment of 50 RS units.
Paik et al. N Engl J Med. 2004;351:2817-2826.
17
Oncotype DX®
Clinical Validation:
The Kaiser Permanente Study
Habel et al. Breast Cancer Res. 2006;May 31;8(3):R25.
The Kaiser Permanente Study:
Methods
Study Design
Matched Case-Control
Study Population
Kaiser Permanente patients <75 yr in 14 Northern
California hospitals diagnosed with node-negative
BC 1985-94, no chemotherapy (N = 4964)
Cases: Deaths from BC (n = 220)
Controls: Randomly selected, matched on age,
race, diagnosis year, KP facility, tamoxifen (n = 570)
Data Sources
Cancer registry, medical records, archived
diagnostic slides, and tumor blocks
Habel et al. Breast Cancer Res. May 2006.
19
The Kaiser Permanente Study:
Risk of BC Death at 10 Years: ER+, Tam+ Patients
Risk Classifier
Recurrence Score
Low (<18)
Intermediate (18-30)
High (>31)
1Based
10-yr
Absolute
Risk1
Kaiser
10-yr
Absolute
Risk
NSABP B14
2.8%
10.7%
15.5%
3.1%
12.2%
27.0%
on methods by Langholz and Borgan, Biometrics 1997;53:767-774.
Habel et al. Breast Cancer Res. May 2006.
20
The Kaiser Permanente Study:
Conclusions
• “The RS has now been shown to be strongly
associated with risk of breast cancer-specific
mortality among LN–, ER+, tam-treated patients
participating in a clinical trial and among similar
patients from the community setting.”
• “Combining Recurrence Score, tumor grade,
and tumor size provides better risk classification
than any one of these factors alone.”
Habel et al. Breast Cancer Res. May 2006.
21
Oncotype DX®
Prediction of Tam Benefit:
NSABP B-14 Placebo and
Tamoxifen Arms*
*Paik et al. ASCO 2004. Abstract #510.
Tamoxifen Benefit and Oncotype DX™
NSABP B-14 Tam Benefit Study in N–, ER+ Patients
Design
Placebo-Eligible
Randomized
Tam-Eligible
Objective: Determine whether the 21-gene RS assay
provides predictive information for patients who were
treated with tamoxifen (likelihood of recurrence)
Paik et al. ASCO 2004. Abstract #510.
23
B-14 Overall Benefit of Tamoxifen
All Patients (N = 645)
Proportion without Distant Recurrence
1.0
0.9
0.8
0.7
0.6
0.5
0.4
0.3
0.2
Placebo
Tamoxifen
0.1
0.0
0
2
4
6
8
10
12
14
16
Years
Paik et al. ASCO 2004. Abstract #510.
24
B-14 Benefit of Tamoxifen
By Recurrence Score Risk Category
Proportion without Distant Recurrence
1.0
0.8
0.6
0.4
Low Risk (RS<18)
N
171
Placebo
Tamoxifen 142
0.2
0.0
0
2
4
6
8
10
12
14
16
0.8
0.6
0.4
Int Risk (RS 18-30)
N
85
Placebo
Tamoxifen 69
0.2
0.0
0
2
4
6
8
Years
Proportion without Distant Recurrence
Proportion without Distant Recurrence
1.0
10
12
14
16
Years
1.0
Interaction P = 0.06
0.8
0.6
0.4
High Risk (RS≥31)1
0.2
Placebo
Tamoxifen
1
N
99
79
The results should not be
used to conclude that
tamoxifen should not be
given to the high-risk group
0.0
0
2
4
6
8
Years
10
12
14
16
Paik et al. ASCO 2004. Abstract #510.
25
Analysis of Placebo and Tam-Treated
Patients in NSABP B-14
• Results
– Subset of Oncotype DX® genes is prognostic
• 5 proliferation genes
– Cyclin B1, Ki-67, MYBL2, Survivin, STK15
• PR
– Quantitative measurement of the ER gene
expression by the Oncotype DX® assay
predicts the benefit of tamoxifen
– Quantitative ER and Recurrence Score are
only modestly correlated
Paik et al. ASCO 2004. Abstract #510.
26
Analysis of Placebo and Tam-Treated
Patients in NSABP B-14
• Conclusions
– RS combines prognostic and predictive
factors into one assay report
– RS performance is derived from
measurement of expression of each of the 21
genes on a continuous scale with high
precision and reproducibility
Paik et al. ASCO 2004. Abstract #510.
27
Oncotype DX®
Prediction of Chemo Benefit:
NSABP B-20 Study*
*Paik et al. J Clin Oncol. 2006;24:3726-3734
Chemotherapy Benefit and Oncotype DX®
NSABP B-20 Chemo Benefit Study in N–, ER+ Pts
Design
Tam + MF
Randomized
Tam + CMF
Tam
Objective:
Determine the magnitude of the chemo
benefit as a function of the 21-gene RS assay
Paik et al. J Clin Oncol. 2006;24:3726-3734.
29
B-20 Results
Tam vs Tam + Chemo – All 651 Patients
Proportion without Distant Recurrence
1.0
0.9
0.8
0.7
4.4% absolute
benefit from
tam + chemo
at 10 years
0.6
0.5
0.4
0.3
0.2
All Patients
N
424
227
Tam + Chemo
Tam
0.1
Events
33
31
P = 0.02
0.0
0
2
4
6
Years
8
10
12
Paik et al. J Clin Oncol. 2006.
30
1.0
1.0
0.9
0.9
0.8
0.8
0.7
0.7
Low RS
p = 0.61
0.6
DRFS
0.6
0.5
0.4
0.3
0.2
TAM +(RSChemo
Low Risk Patients
< 18)
Tam +
Chemo
TAM
Tam
0.1
218
135
Int Risk Patients (RS 18-30)
N Events
0.3
0.2
8
4
p = 0.39
Int RS
0.5
0.4
Low Risk Patients (RS<18)
N Events
TAM + Chemo
TAM
89
45
Int Risk (RS 18 - 30)
Tam + Chemo
Tam
0.1
9
4
0.0
0.0
0
2
4
6
8
10
0
12
2
4
6
8
10
12
Years
Years
1.0
0.9
28% absolute
benefit from
tam + chemo
0.8
0.7
High RS
0.6
DRFS
Distant Recurrence
Proportion withoutDRFS
B-20 Results: Tam vs Tam + Chemo
p < 0.001
0.5
0.4
High Risk Patients (RS≥31)
N Events
0.3
0.2
High Risk Patients (RS  31)
Tam + Chemo
Tam
TAM + Chemo
TAM
0.1
117
47
13
18
0.0
0
2
4
6
8
10
12
Years
Paik et al. J Clin Oncol. 2006.
31
B-20 Results: Absolute % Increase in Proportion
Distant Recurrence-Free at 10 Years
n = 353
Low
RS <18
n = 134
Int
RS 18-30
n = 164
High
RS ≥31
0
10%
20%
30%
40%
% Increase in Proportion Distant Recurrence-Free at 10 Yrs
Paik et al. J Clin Oncol. 2006.
(mean ± SE)
32
Summary of Treatment Benefit Related to RS
and Breast Cancer Death in NSABP B-14 and B-20
Low Risk (RS < 18)
Intermediate Risk (RS 18 - 30)
HIgh Risk (RS > 31)
NO SYSTEMIC RX
B14 No Tam
HORMONAL RX
B14 Tam
B20 Tam
HORM + CHEMO
B20 Tam + CT
0
5
10
15
20
25
30
35
10 Yr Absolute Risk BC Death (%) (95% CI)
40
33
Largest Tamoxifen Benefit Observed in Low- and
Intermediate-Risk Recurrence Score Groups
Low Risk (RS < 18)
Intermediate Risk (RS 18 - 30)
HIgh Risk (RS > 31)
NO SYSTEMIC RX
B14 No Tam
TAMOXIFEN
BENEFIT
HORMONAL RX
B14 Tam
B20 Tam
HORM + CHEMO
B20 Tam + CT
0
5
10
15
20
25
30
35
10 Yr Absolute Risk BC Death (%) (95% CI)
40
34
Largest Chemotherapy Benefit Observed in
High-Risk Recurrence Score Group
Low Risk (RS < 18)
Intermediate Risk (RS 18 - 30)
HIgh Risk (RS > 31)
NO SYSTEMIC RX
B14 No Tam
HORMONAL RX
B14 Tam
B20 Tam
HORM + CHEMO
CHEMOTHERAPY
BENEFIT
B20 Tam + CT
0
5
10
15
20
25
30
35
40
10 Yr Absolute Risk BC Death (%) (95% CI)
35
Standardized Quantitative
Oncotype DX Assay
Recurrence Score in N-, ER+ patients
40%
Intermediate
Risk Group
Distant Recurrence at 10 Years
Low Risk Group
35%
High Risk Group
30%
25%
20%
15%
10%
5%
0%
0
5
10
15
20
25
30
35
40
45
50
Recurrence Score
Lower RS’s
•Lower likelihood of recurrence
•Greater magnitude of TAM benefit
•Minimal, if any, chemotherapy benefit
Higher RS’s
•Greater likelihood of recurrence
•Lower magnitude of TAM benefit
•Clear chemotherapy benefit
1) Paik et al NEJM 2004, 2) Habel et al Breast Cancer Research 2006
3) Paik et al JCO 2006, 4) Gianni et al JCO 2005
36
Correlation of RS with traditional
prognostic factors including age,
tumor size, and tumor grade
Results from NSABP B20 Results
NSABP B20 Results: Many Younger Patients
Have Low Recurrence Scores
p=0.018
100
Recurrence.Score
Recurrence
Score
80
60
40
41%
24%
28%
19%
14%
21%
22%
21%
44%
55%
50%
60%
20
0
N=63
N=226
N=166
N=196
A:<40
< 40
B:40-49
40
- 49
C:50-59
50
- 59
D:>=60
≥ 60
Age
Patient Age
Paik et al. J Clin Oncol. 2006. 38
NSABP B20 Results: Many Small Tumors
Have Intermediate to High RS
p=0.001
100
Recurrence
Score
Recurrence.Score
80
60
40
20
16%
25%
30%
33%
20%
19%
23%
21%
64%
56%
46%
46%
0
N=110
A:<=
1cm
≤ 1 cm
N=318
N=196
B:1.1-2.0cm
C:2.1-4.0cm
1.1 - 2 cm
2.1 - 4 cm
Clinical.Tumor.Size
N=24
D:>=
> 44.1cm
cm
Clinical Tumor Size
Paik et al. J Clin Oncol. 2006. 39
NSABP B20 Results: Significant Proportion of
High-Grade Tumors Have Low RS
Grading by pathologist at local clinical trial site
p<0.001
100
Grading by pathologist at central lab
60
40
20
p<0.001
100
12%
22%
42%
16%
22%
22%
73%
56%
36%
0
N=77
N=339
N=163
A:Well
Well
B:Moderate
Moderate
Tumor.Grade.A
C:Poor
Poor
80
Recurrence.Score
Recurrence
Score
Recurrence.Score
Recurrence
Score
80
60
40
20
5%
12%
61%
12%
24%
19%
83%
64%
19%
Tumor Grade (Site)
0
N=119
Well
A:Well
N=340
Moderate
B:Moderate
Tumor.Grade.C
N=190
Poor
C:Poor
Tumor Grade (Pathologist B)
Paik et al. J Clin Oncol. 2006. 40
Prospective multi-center study of the impact of the
21-gene Recurrence Score (RS) assay on medical
oncologist (MO) and patient (pt) adjuvant breast
cancer (BC) treatment selection
Shelly S. Lo1, John Norton1, Patricia B. Mumby1, Jeffrey
Smerage2, Joseph Kash3, Helen K. Chew4, Daniel Hayes2,
Andrew Epstein5, Kathy S. Albain1
1Loyola
University, Maywood IL, 2University of Michigan,
Ann Arbor MI, 3Edward Hospital, Naperville IL, 4UC Davis,
Sacramento CA, 5Mount Sinai Medical Center, New York NY
ASCO 2007, Abstract #577
Background
• There is little data regarding the impact of
the RS on medical oncologist (MO) and
patient (pt) decision making. A multicenter study was designed to
prospectively examine whether the RS
can affect MO and pt adjuvant treatment
selection.
ASCO 2007, Abstract #577
42
Methods
• 17 MOs at 1 community and 3 academic practices
participated. Each participating MO consecutively
offered enrollment to eligible women with N-, ER+ BC.
• Each participating MO and consenting patient
completed pre- and post-RS assay questionnaires.
• MOs stated their adjuvant treatment recommendation
and confidence in it pre and post RS assay.
• Pts indicated treatment choice pre and post RS assay.
In addition, patients completed measures for quality of
life, anxiety, and decisional conflict pre and post assay.
• RS assay results were returned to MO and shared with
pt for routine clinical care.
ASCO 2007, Abstract #577
43
Change in MO Treatment
Recommendation by RS
MO
Pre-RS
Post- RS
Treatment
Recomm.
Number (%) Mean RS
CHT
HT alone
Equipoise
42 (47.2%)
46 (51.7%)
1 (1.1%)
21
18
19
Number
(%)
23 (25.8%)
Mean
RS
29
60 (67.4%)
6 (6.7%)
16
19
ASCO 2007, Abstract #577
44
MO Treatment Recommendations
Changed 31.5% of the Time
MO Pre to Post-RS Assay
Treatment Recommendation
Number of Cases(%)
CHT to HT
20 (22.5)
HT to CHT
3 (3.4)
CHT or HT to Equipoise
5 (5.6)
Treatment plan did not
change
61 (68.5)
Total
89 (100)

Treatment recommendation changed for 28 (31.5%) cases after
results of RS Assay known.

The most common change was from a recommendation of CHT
to HT in 22.5% of cases
ASCO 2007, Abstract #577
45
Other Findings
• Confidence was increased in 76% of the MO
recommendations.
• RS Assay impacted patient adjuvant treatment
decisions
• 95% of patients were glad they had the test performed
• 12 (13.5%) patient treatment decisions did not match
their MO treatment recommendation. This may be due
to:
– Patients choosing different treatment option than that
recommended
– Inadequate communication between MOs and pts
– Patient misunderstanding of survey question
ASCO 2007, Abstract #577
46
Conclusions
• RS Assay changed physician adjuvant treatment
recommendation 31.5% of the time
• Results from the RS assay were associated with less
adjuvant chemotherapy administration
– The most common treatment recommendation
change for MO was changing recommendation from
CHT to HT in 22.5% of cases
– Of the 6 pts whose physicians thought their RS
represented equipoise, 1 pt chose chemotherapy,
3 chose HT, 1 chose observation, and 1 understood
the concept of equipoise.
• Results of the RS Assay increased physician confidence
in treatment recommendation
ASCO 2007, Abstract #577
47
TAILORx
(PACCT-1 Trial)
Sponsored by NCI
Administered by ECOG
Participating cooperative groups include
ECOG, SWOG, NCCTG, CALGB, NCIC,
ACOSOG, and NSABP
Trial Assigning IndividuaLized Options for
Treatment (Rx) (TAILORx)
• Premise
– Integration of a molecular profiling test (Oncotype DX®)
into the clinical decision-making process
• Potential Implications
– Reduce chemotherapy overtreatment in those likely to
be appropriately treated with hormonal therapy alone
– Reduce inadequate treatment by identifying individuals
who derive great benefit from chemotherapy
– Evaluate benefit of chemotherapy where uncertainty
still exists about its utility
49
TAILORx: Scientific Rationale for
NCI and Breast Intergroup Selecting
Oncotype DX® Assay for First PACCT trial
1. Validated prognostic test for tamoxifen-treated patients
– Predictive of distant recurrence
– May be used as categorical or continuous variable
– Paik et al. NEJM, 2004
2. Also validated in population-based Kaiser study
– Habel et al. Breast Cancer Research, May 2006
3. Lower RS predictive of tamoxifen benefit
– Paik et al. ASCO 2005, abstr 510
4. Higher RS predictive of chemotherapy benefit
– Paik et al. JCO, August 2006
5. Correlates more strongly with outcome than Adjuvant!
– Bryant et al. St. Gallen, 2005
6. Predictive of local recurrence in tam-treated patients
– Mamounas, SABCS 2005, abstr 29
Sparano, Clinical Breast Cancer, 2006
Sparano, ASCO Educational Book 2007
50
40%
Intermediate
Risk Group
Distant Recurrence at 10 Years
Low Risk Group
35%
High Risk Group
TAILORx Primary
Study Group
30%
25%
20%
15%
10%
5%
0%
0
5
10
15
20
25
30
35
40
45
50
Recurrence Score
51
Schema: TAILORx
Node-Neg, ER-Pos Breast Cancer
Register
Specimen
banking
Oncotype DX® Assay
RS 11-25
RS <10
Hormone
Therapy
Registry
Randomize
Hormone Rx
vs
Chemotherapy
+ Hormone Rx
RS >25
Chemotherapy
+
Hormone Rx
Primary study group
52
Study Design: Primary Objectives
• To determine whether adjuvant hormonal therapy
(ie, experimental arm) is not inferior to adjuvant
chemohormonal (standard arm) for patients in the
“primary study group” (Oncotype DX® RS 11-25)
• To create a tissue and specimen bank for patients
enrolled in this trial to learn more about breast
cancer
53
TAILORx: Key Points
• Participating groups
– ECOG, SWOG, NCCTG, CALGB, NCIC, ACOSOG, and NSABP
• Adjuvant therapy
– Choice of hormonal and/or chemotherapy regimen is at
discretion of treating physician
• Other trials
– May enroll on other CTSU or other cooperative group studies
if treatment assignment on other trial is consistent
• Payment for the Oncotype DX Assay
– Genomic Health will assist in securing reimbursement for
patients who have health insurance
– By agreement with NCI to avoid bias in enrollment in the trial,
patients who are uninsured or who have copayments or
deductibles will not be responsible for the cost of the
Oncotype DX®
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Oncotype DX® Extensively Studied:
Study Experience in >3300 Patients
Study
Type
No. Pts
Providence
Exploratory
136
Rush*
Exploratory
78
NSABP B-20
Exploratory
233
NSABP B-14*
Prospective
668
MD Anderson*
Prospective
149
Prospective Case-Control
790 Cases/Controls
Prospective Placebo vs Tam
645
Exploratory
89
NSABP B-20*
Prospective Tam vs Tam+Chemo
651
ECOG 2197*
Exploratory and Prospective
776
SWOG 8814
Prospective Tam vs Tam+Chemo
367
Kaiser Permanente*
NSABP B-14
Milan*
*Published studies
55
Conclusions
Recurrence Score in N-, ER+ patients
Lower RS’s
Higher RS’s
• Lower likelihood of recurrence
• Greater likelihood of recurrence
• Greater magnitude of TAM benefit
• Lower magnitude of TAM benefit
• Minimal, if any, chemotherapy benefit • Clear chemotherapy benefit
1) Paik et al NEJM 2004, 2) Habel et al Breast Cancer Research 2006
3) Paik et al JCO 2006, 4) Gianni et al JCO 2005
56
Genomic Health Today
• Physician Usage and Adoption
– 65,000+ Oncotype DX® test results delivered*
– >7,500 physicians have ordered the test*
• Reimbursement for Oncotype DX
– Coverage for Medicare patients
– Coverage >90% of privately insured lives
*As of August 5, 2008
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Conclusions
• The Oncotype DX® Recurrence Score assay
predicts the likelihood of adjuvant
chemotherapy benefit
• It also is a prognostic assay for the risk of
distant recurrence at ten years assuming five
years of adjuvant tamoxifen treatment
• Oncotype DX® Recurrence Score assay
shows consistent results across multiple
independent studies
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