1. Oncotype Dx® Breast Cancer Assay
and impact on treatment decisions
Noa Efrat (Ben-Baruch), MD
Kaplan Medical Center
Rehovot, Israel

2. 2
Oncotype in Israel
• Number of tests 8458
• Node Negative 6256
• Node positive 2080
– N mic 828
– 1 node 806
– 2 nodes 280
– 3 nodes 121
– Other 45

3. 3
IMPACT
Pa#ent
Physician
Society

4. 4
• Impact on treatment selection - DATA
• Impact on patients’ and physicians’
confidence in treatment selection - DATA
• Impact on patient outcome – some DATA
• Impact on early costs - DATA
– Cost of test, cost of therapy, AE’s, social
• Impact on late costs – no DATA
– recurrence
IMPACT

5. 5
IMPACT
Pa#ent
Physician
Society
Maximal
Impact

6. 6
Assessing the Utility of the Oncotype DX® Breast
Cancer Assay in Decision Impact Studies
Treating physician
Treatment recommendation and level of confidence
Patient
Decisional conflict scale
Adjuvant treatment actually administered
Oncotype DX® Recurrence Score Assay
Status Pre-Oncotype DX
Status Post-Oncotype DX
Treating physician
Treatment recommendation and level of confidence
Patient
Decisional conflict scale

7. 7
Case Report
• 55 years old, pharmacist
• Post menopausal
• Diagnosed in April 2006 with Tubular/invasive duct
carcinoma, grade II, no LVI
• ER/PR positive (+2), HER2 negative
• Tumor size – 1.0 cm, good margins
• 7 negative nodes
T1b N0 M0

8. 8
• Node negative, receptor positive breast
cancer
– Low risk of metastases
– What is the optimal adjuvant therapy?
– Avoid over treatment
The Spectrum of Early Breast Cancer

9. 9
• Impact on treatment selection - DATA
• Impact on patients’ and physicians’
confidence in treatment selection - DATA
• Impact on patient outcome – some DATA
• Impact on early costs - DATA
– Cost of test, cost of therapy, AE’s, social
• Impact on late costs – no DATA
– recurrence
IMPACT

10. 10
Treatment Alterations:
Rx pre-RS vs. Rx post-RS
N = 313
Chemo ---> HT
33.5%
HT ---> Chemo
6.4%
No Change
60.1%
Impact of RS on Treatment Choice
Ben-Baruch N, et al. J Clin Oncol. 2007;25(18S): Abstract 11008.
Klang S, et al. Value in Health 2010 Jun-Jul;13(4):381-7
• CHS is the largest HMO in
Israel.
• Oncotype DX® was
introduced to its services in
2006.
• Prospective gathering of
data regarding treatment
choice pre and post RS
results was built in the
application form.

11. Impact of the Oncotype DX® Breast Cancer Assay
in N0, ER+ EBC
Prospective Decision Impact Studies from Various Countries
#1-3 positive lymph nodes, HT only endocrine therapy, CHT chemoendocrine therapy
1Lo S, et al. J Clin Oncol. 2010. 2Albanell et al. Ann Oncol 2011, 3Eiermann et al. Ann Oncol 2012 in press, 4Yamauchi et al. ESMO 2011,
5De Boer et al. SABCS 2011, 6Davidson JA et al. ASCO 2012, 7Holt S et al., St. Gallen 2011, #P196, 8Gligorov J et al. ASCO 2012
Study N Change rate from pre- to
post-Oncotype DX®
breast cancer assay
CHT to
HT
HT to
CHT
US Study1 (N0) 89 31.5% 22.5% 3.4%
Spanish Study2 (N0) 107 31.8% 20.6% 11.2%
German Study3 (N0) 244 30.3% 18.4% 11.5%
Japanese Study4 (N0) 73 30.1% 27.4% 2.7%
Australian Study5 (N0) 101 22.8% 11.9% 10.9%
Canadian Study6 (N0) 150 30% 20% 10%
UK Study7 (N0, N1itc, N1mic) 142 26.8% 18.3% 8.5%
French Study8 (N0, N1mic) 96 36% 31% 5%

12. 12
Metaanalysis of 9 clinical utility studies
(7 retrospective, 2 prospective) with total n=1154 ER+, N0 EBC patients
42%
58%
Chemo + hormonal therapy
Hormonal therapy only
Overall, the RS led to a 36% change in
treatment decisions
• 30% from CT+HTà HT
• 6% from HT à CT+HT
Hornberger J, et al. St. Gallen 2011. #P201.
6% change
Recommendation after RS
in patients with
initial HT recommendation
Treatment plan before the
Oncotype DX breast cancer assay
30% change
Recommendation after RS
in patients with
initial CHT recommendation

13. 13
– Treatment selection was changed in
~30% of patients
– Most were spared chemotherapy
– 6% were given adjuvant chemotherapy
because of RS determination – CURE?
Node negative, receptor positive
early breast cancer

14. 14
• Node positive, receptor positive breast
cancer
– Higher risk of metastases
– Do all patients need adjuvant chemotherapy?
– Avoid overtreatment
The Spectrum of Early Breast Cancer

15. 15

16. 16

17. Oncotype DX® testing has caused a shift in the
treatment paradigm for
N+, ER+, breast cancer patients in Israel
• Results from a retrospective study in 951 patients from 4 medical centers in Israel
Ø Overall, 24.1% of Oncotype DX® assay patients and 70.1% of controls received
chemotherapy (adjusted odds ratio, 0.169; p<.0001; adjusted for age, tumor size,
grade, and nodal status).
Ø Testing led to a reduction of chemotherapy use by 45.6% in node-positive disease
Stemmer et al. EBCC 2012.

18. Use of Oncotype DX reduced chemotherapy use in
patients with node-positive EBC by age, tumor size,
grade, and nodal status
Age Group
Nodal StatusGrade
Tumor Size
Stemmer et al. EBCC 2012.
Oncotype DX
Overall
by RS group
Controls

19. 19
Decision Impact Studies Overview of Results
from Different Countries
*retrospective data, 1-3 positive nodes HT hormonal therapy only, CHT chemohormonal therapy
1Lo S, et al. J Clin Oncol. 2010. 32Albanell et al. Ann Oncol 2011, 3Rezai et al. SABCS 2011, 5 Yamauchi et al. ESMO
2011, 5 De Boer et al. SABCS 2011, 6 Hornberger et al. St. Gallen, #P201, 4 Holt S et al., St. Gallen 2011, #P196, 6
Hornberger et al. St. Gallen, #P201, 8Oratz et al. J Oncol Pract 2011
Study N
Change Rate
pre- to post-Oncotype DX
CHT to
HT
HT to
CHT
US study1 (N0) 89 31.5% 22.5% 3.4%
Spanish study2 (N0) 107 31.8% 20.6% 11.2%
German study3 (N0) 244 30.3% 18.4% 11.5%
Japanese study4 (N0) 73 30.1% 27.4% 2.7%
Australian study5 (N0) 101 22.8% 11.9% 10.9%
Meta-analysis6 (N0) 1154 35% 30% 5%
UK study7 (N0, N1itc, N1mic) 142 26.8% 18.3% 8.5%
German study3 (N+#) 122 38.5% 27.9% 9.0%
Japanese study4 (N+#) 17 70.6% 70.6% 0%
Australian study5 (N+#) 50 26% 24% 2%
US study8 (N+)* 138 50.7% 33.3% 9.4%
19

20. 20
• Impact on treatment selection - DATA
• Impact on patients’ and physicians’
confidence in treatment selection - DATA
• Impact on patient outcome – some DATA
• Impact on early costs - DATA
– Cost of test, cost of therapy, AE’s, social
• Impact on late costs – no DATA
– recurrence
IMPACT

21. Physicians’ perspective
21

22. US Study: Impact of Recurrence Score on Physicans’
Confidence in Treatment Recommendations
Physicians’ answers to question “I am more confident in my treatment
recommendation after ordering the Oncotype DX® assay”
Post-RS
Lo S, et al. J Clin Oncol. 2010, 28:1671-6. 22

23. Changes
in
Physician
Confidence
from
Pre-­‐
to
Post-­‐Oncotype
DX
(n=96)
Pre:
I
am
confident
in
my
treatment
recommenda?on
prior
to
ordering
the
Oncotype
DX
assay.
Post:
I
am
confident
in
my
treatment
recommenda?on
aBer
ordering
the
Oncotype
DX
assay.
1
=
Strongly
disagree
2
=
Disagree
3
=
Neither
disagree
nor
agree
4
=
Agree
5
=
Strongly
agree
23
Pre
Oncotype
DX
(%)
Post
Oncotype
DX
(%)
Strongly
confident
(5)
27
43
Confident
(4)
48
47
Ambivalent
(3)
18
7
Not
confident
(2)
6
1
Not
at
all
confident
(1)
0
1
Gligorov
et
al.
ASCO
2012

24. 45,1 44,7 45,9
45,1 46,3 42,6
9,3 8,2 11,5
0
20
40
60
80
100
120
Overall
(n=366)
Node
negative
(n=244)
Node
positive
(n=122)
Not
assessable
Confidence
dropped
Confidence
remained
unchanged
Confidence
increased
p=0.047 p=0.0278 p=0.8157
German Study: Changes in physicians‘ confidence in
treatment recommendation pre- to post-Oncotype DX®
• Physicians had the choice between absolute, high,
intermediate and low to rate their level of confidence
Rezai M et al. SABCS 2011, #P2-12-26. 24

25. Patients’ perspective
25

26. US Decision Impact Study
Knowledge of RS decreases Patients’ Situational Anxiety
State Anxiety P=0.007
Trait Anxiety P=0.272
Lo S, et al. J Clin Oncol. 2010;28:1671-6.
• Patients reported significantly lower conflict about the decision for
adjuvant treatment
• They also reported greater satisfaction with decision making, decreased
situational anxiety and lower perceived risk of recurrence after learning
the results of the RS assay.
• 81% of patients said results influenced their treatment decision
26

27. 27
• Impact on treatment selection - DATA
• Impact on patients’ and physicians’
confidence in treatment selection - DATA
• Impact on patient outcome – some DATA
• Impact on early costs - DATA
– Cost of test, cost of therapy, AE’s, social
• Impact on late costs – no DATA
– recurrence
IMPACT

28. 28

29. 29
Results
• 751 patients with low-intermediate risk
according to traditional parameters.
– 38% intermediate RS – 13% received CTX
– 8% high risk – 61% received CTX
• Median follow up - 26 months
– No systemic recurrences
• Short follow up, no decision change data

30. 30
• Ongoing, continuously updated, gathering
of data on all CHS patients with early
breast cancer who had oncotype DX®
done
– As of this year >5000 patients
– Median follow up > 4 years
• Study the relationship between RS,
clinico-pathological parameters, actual
treatment given and recurrence
• IRB Submission completed
Impact of RS on treatment outcome
CHS data base

31. 31
• Impact on treatment selection - DATA
• Impact on patients’ and physicians’
confidence in treatment selection - DATA
• Impact on patient outcome – some DATA
• Impact on early costs - DATA
– Cost of test, cost of therapy, AE’s, social
• Impact on late costs – no DATA
– recurrence
IMPACT

32. 32
Value of Oncotype DX® BC Assay to the
Healthcare System – Klang et al
Klang SH, et al. Value Health. 2010 Apr 15. [Epub ahead of print]. 32

33. Consistent cost effectiveness with Oncotype
DX® across countries
Citation Reported Findings
(ICER in Cost per
QALY gained with
Oncotype DX)
Country
Threshold
(willingness to
pay for 1 QALY)
Country Comment
Davidson et al. 2013 CAD 6,630 CAD 75,000 Canada ü Cost Effective
Lacey et al. 2011 EUR 9,462 EUR 20,000 Ireland ü Cost Effective
Hall et al. 2011 GBP 5,529 GBP 20,000 UK ü Cost Effective
Holt et al. 2011 GBP 6,232 GBP 20,000 UK ü Cost Effective
Klang et al. 2010 USD 10,700 USD 35,000 Israel ü Cost Effective
Kondo et al. 2010 USD 3,848 USD 50,000 Japan ü Cost Effective
Lamond et al. 2012 CAD 9,591 CAD 75,000 Canada ü Cost Effective
Madaras et al. 2011 EUR 9,730
EUR
12,600-25,300
Hungary ü Cost Effective
O’Leary et al. 2010 AUS 9,986 AUS 18,000 Australia ü Cost Effective
Paulden et al. 2011 >CAD 29,000 CAD 75,000 Canada ü Cost Effective
Tsoi et al. 2010 CAD 63,421 CAD 75,000 Canada ü Cost Effective
Vanderlaan et al. 2011
Improved outcomes (QALYs)
Reduced costs
USA ü Cost Saving
De Lima Lopez et al.
2011
Singapore ü Cost Saving
Cosler et al. 2009 USA ü Cost Saving
Blohmer et al. 2012 Germany ü Cost Saving
Valtaire et al. 2012 France ü Cost Saving
Hornberger et al. 2011 USA ü Cost Saving
Hornberger et al. 2005 USA ü Cost Saving
Lyman et al. 2007 USA ü Cost Saving

34. 34
Case Report
• 55 years old, pharmacist
• Post menopausal
• Diagnosed in April 2006 with Tubular/invasive duct carcinoma,
grade II, no LVI
• ER/PR positive (+2), HER2 negative
• Tumor size – 1.0 cm, good margins
• 7 negative nodes
T1b N0 M0
RS -31
Adj chemotherapy, hormonal and XRT
Alive and well

35. Conclusions
• Results of decision impact studies are very
consistent across different countries
- ~30% change in treatment recommendations after
Oncotype DX® for node negative patients, and clinically
relevant also in node-positive disease
- Treatment recommendations followed the Recurrence
Score result
- Intermediate Recurrence Score also provides clinically
relevant information
- Use of the Recurrence Score result led to a clinically
significant reduction in chemotherapy use

36. Conclusions
• Testing with the Oncotype DX® breast cancer assay
increased confidence of physicians and of patients
in adjuvant therapy decision-making.
•
• Prospective outcome data is sparse.
• Consistent cost effectiveness with Oncotype DX®
across countries

37. 37
This is the DNA
sequence of my
tumor
Biology
has
spoken,
and
we
should
listen
George
W.
Sledge
Jr.,
ASCO
2005