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

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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

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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

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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

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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

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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

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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

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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

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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

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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

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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 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

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This is the DNA sequence of my

tumor

Biology  has  spoken,  and    we  should  listen

George  W.  Sledge  Jr.,    ASCO  2005