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Oncotype Dx® Breast Cancer Assay and impact on treatment decisions
Noa Efrat (Ben-Baruch), MD Kaplan Medical Center Rehovot, Israel
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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
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IMPACT
Pa#ent
Physician
Society
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
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IMPACT
Pa#ent Physician
Society
Maximal Impact
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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
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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
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• 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
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• 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
Treatment Alterations: Rx pre-RS vs. Rx post-RS
N = 313
Chemo ---> HT33.5%
HT ---> Chemo6.4%
No Change60.1%
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.
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%
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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
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– 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
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• Node positive, receptor positive breast cancer – Higher risk of metastases – Do all patients need adjuvant chemotherapy? – Avoid overtreatment
The Spectrum of Early Breast Cancer
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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.
Use of Oncotype DX reduced chemotherapy use in patients with node-positive EBC by age, tumor size,
grade, and nodal status
Age Group
Nodal Status Grade
Tumor Size
Stemmer et al. EBCC 2012.
Oncotype DX Overall by RS group Controls
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%
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• 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
Physicians’ perspective
21
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
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
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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
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 remainedunchangedConfidence 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
Patients’ perspective
25
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
• 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
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
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• 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
• 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
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
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
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
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
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
This is the DNA sequence of my
tumor
Biology has spoken, and we should listen
George W. Sledge Jr., ASCO 2005
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