/
Adjuvant Therapy of Breast Cancer Adjuvant Therapy of Breast Cancer

Adjuvant Therapy of Breast Cancer - PowerPoint Presentation

marina-yarberry
marina-yarberry . @marina-yarberry
Follow
364 views
Uploaded On 2019-02-13

Adjuvant Therapy of Breast Cancer - PPT Presentation

Christy A Russell MD Keck School of Medicine University of Southern California Hazard Rate of Relapse According to Tumor Subtype and Year of Diagnosis British Columbia PopulationBased Data 19861992 ID: 751648

chemotherapy ofs tamoxifen therapy ofs chemotherapy therapy tamoxifen women breast cancer patients 2014 soft endocrine risk years premenopausal node

Share:

Link:

Embed:

Download Presentation from below link

Download Presentation The PPT/PDF document "Adjuvant Therapy of Breast Cancer" is the property of its rightful owner. Permission is granted to download and print the materials on this web site for personal, non-commercial use only, and to display it on your personal computer provided you do not modify the materials and that you retain all copyright notices contained in the materials. By downloading content from our website, you accept the terms of this agreement.


Presentation Transcript

Slide1

Adjuvant Therapy of Breast Cancer

Christy A Russell, MDKeck School of MedicineUniversity of Southern CaliforniaSlide2

Hazard Rate of Relapse

According to Tumor Subtype and Year of DiagnosisBritish Columbia Population-Based Data

1986-1992

2004-2008

Cossetti

, et al. JCO 2014Slide3

What’s New in Chemotherapy?Slide4

What’s New with Chemotherapy?

ER (+), HER2 (-) Breast CancerWe await the publication of TAILORx to further refine the predictive value of Oncotype Dx (especially in the intermediate RS tumors).We await the publication of MINDACT trial to elicit whether MammaPrint has any predictive value at all over clinical features for chemotherapy benefit.

We await completion of the

RxPonder

trial for ER(+), lymph node (+) patients.Slide5

TAILORx

schema Trial Assigning Individual

ized

O

ptions for Treatment

Patients with node-negative, hormone-positive breast cancer

Onco

type

DX

®

assay

Recurrence Score

®

result ≤ 10

Hormone therapy registry

Recurrence Score result 11-25*

Randomize to either hormone therapy or chemotherapy + hormone therapy

Recurrence Score result > 25Chemotherapy + hormone therapy

Register specimen banking

*

Primary study group

:

Recurrence Score result 11-25 correlates with

a 10-20% risk of distance recurrence at 10 years (upper 95% CI)Slide6

EORTC-BIG MINDACT TRIAL DESIGN

6,000 Node negative and 1-3 + lymph node breast cancer women

Dr Martine Piccart-Gephart JBI, Brussels

Evaluate Clinical-Pathological risk

and

70-gene signature risk

Clinical-pathological and 70-gene both HIGH risk

Discordant cases

Clin-Path HIGH

70-gene LOW

Clinical-pathological and 70-gene both LOW risk

Use Clin-Path risk to decide Chemo or not

Use 70-gene risk to decide Chemo or not

Adjuvant

Chemotherapy

(+ endocrine Tx if ER+)

N=3300 (55%)

N=600 (10%)

Adjuvant Endocrine

therapy only

N=2100 (35%)

Clin-Path LOW

70-gene HIGH

Randomize

The goal of this trial is to show that MammaPrint can

spare 20-30% of patients from adjuvant chemoSlide7

RxPonder

Schema and Patient Flow

Node-positive (1-3 nodes) HR-positive and HER2-negative breast cancer

(N= 600)

RS already Available

Physician and patients discuss randomization knowing the RS

(N= 8,800)

Patients consent to study-sponsored RS testing, discussion of potential trials, tumor tissue submission and linkage to cancer registry data

RECURRENCE SCORE

(N= 3,800)

Discuss alternative trials for high risk patients

N= 5,600

Physician and patients discuss randomization knowing the RS

N= 1,600

Record chosen therapy and followed for vital status through cancer registry

N= 2,000

Chemotherapy; appropriate endocrine therapy

N= 2,000

No Chemotherapy; appropriate endocrine therapy

STEP 2 REGISTRATION/

RANDOMIZATION

N= 4,000

Randomization

stratified by

1. RS

0-13 vs. 14-25

2. Menopausal status

3. Axillary node dissection vs. Sentinel node biopsy

RS > 25

RS

<

25

Accept

Refuse

STEP 1 REGISTRATION

Tumor tissue submission for RS

STEP 2 RANDOMIZATIONSlide8

What’s New with Chemotherapy?

ER (-), HER2 (-) Early Breast CancerWhat is the best sequence for anthracyclines and taxanes?Weekly or dose-dense paclitaxel?For whom can we avoid anthracyclines (NSABP B49)?Slide9

CONSORT diagram for the original protocol of Southwest Oncology Group S0221 trial.

Budd G T et al. JCO 2015;33:58-64

©2015 by American Society of Clinical OncologySlide10

(A) Kaplan-Meier disease-free survival plot for all randomly assigned patients by randomization arm.

Budd G T et al. JCO 2015;33:58-64

©2015 by American Society of Clinical Oncology

TN

pts

ER+

ptsSlide11

(A) Kaplan-Meier disease-free survival plot for all randomly assigned patients by randomization arm.

Budd G T et al. JCO 2015;33:58-64Slide12

NSABP B49 Schema

Node Positive, or High-Risk Node Negative,HER2 Negative

Stratification

Number of Positive Nodes

Hormone receptor status

Randomization

Arm 1

Anthracycline-based Chemotherapy*

Arm 2

TC x 6

Chemotherapy per Investigator*

TAC x 6

AC

WPddAC 

WPddAC  ddPSlide13

What’s New for ER (+) Early Breast Cancer in Premenopausal Women?Slide14

Premenopausal HR+ Early Breast Cancer

Adjuvant tamoxifen for > 5 years is recommended.

Genomic profiles are being developed to guide us on which women will benefit from > 5 years of tamoxifen.

The value of ovarian function suppression or ablation for women who receive tamoxifen is uncertain.

Women who develop chemotherapy-induced amenorrhea have a reduced risk of relapse.Slide15

Outcome at 15 years with Tamoxifen

ER+ disease, entry age < 45 years, 79% chemotherapy (n=2614)

EBCTCG, Lancet 2011Slide16

Options for Premenopausal Women

Standard of care has been tamoxifen for 5 years, but > 5 years looks better in some.What is the role of ovarian ablation in women receiving tamoxifen? SOFT

What is the role of ovarian ablation with an AI?

SOFT, TEXT, ABCSG-12Slide17
Slide18

SOFT Primary Analysis: DFS

5.6 years median follow-up

> 95%

Overall

survival

Primary analysis in overall population not significant (p=0.10)

Multivariable Cox model HR=0.78 (95% CI 0.62-0.98) p=0.03

Francis, et al. NEJM 2014Slide19

SOFT Secondary Objectives

T + OFS vs T: 19% relative reduction in breast cancer recurrence p= 0.09

E + OFS vs T: 36% relative reduction in breast cancer recurrence CI (0.49-0.83

)

Francis, et al. NEJM 2014Slide20

SOFT: Outcomes by Chemotherapy

No Prior Chemotherapy

Prior Chemotherapy

No chemotherapy cohort selected for low risk features:

90% > age 40yr, 91% node negative, 85% tumor

<

2 cm, 41% grade 1

Francis, et al. NEJM 2014Slide21
Slide22

Cost of Treatment: Toxicity

15% stopped OFS by 2 years, 22% by 3 years.Provider-reported, clinical importantDepression reported in

50%, 4% severe, 5% increase with OFS

Increase in menopausal symptoms, osteoporosis, insomnia most marked

Patient reportedNo difference in global QOL with use of OFS in primary analysis

Global QOL indicators do not reflect important endocrine effectsEndocrine differences are less pronounced after 2 yearsCompliance or adjustment to menopause?

Endocrine toxicity overall less in women with prior chemotherapy

Ribi

, et al. SABCS 2014Slide23

TEXT and SOFT Trials: Comparison of Tamoxifen or Exemestane With OFS

Tamoxifen

20 mg/day

+

OFS*

(n = 1328)

Premenopausal

Patients with HR+ BC

≤ 12 wks after surgery

(N = 2672)

Stratified by trial, use of chemotherapy, nodal status

*OFS

TEXT: triptorelin 3.75 mg IM every 28 days for 6 mos, then optional bilateral oophorectomy or irradiation

SOFT: choice of method

TEXT

Exemestane 25 mg/day

+

OFS*

(n = 1014)

Tamoxifen

20 mg/day

Premenopausal

patients with HR+ BC

≤ 12 wks after surgery

(if no chemo) or≤ 8 mos after chemo(N = 3066)

SOFT

Tamoxifen

+ OFS*(n = 2344)

Tamoxifen 20 mg/day+ OFS* (n = 1016)Exemestane + OFS*(n = 2346)

Exemestane 25 mg/day+ OFS* (n = 1332)

Joint Analysis

5 yrs

Pagani

O, et al. ASCO 2014. Abstract LBA1.Slide24

60% of first failures involved distant sites, including soft tissue, bone, and viscera

Patients, n

HR (95% CI)

5-Yr DFS, %

E +

OFS

T +

OFS

E + OFS

T +

OFS

All Patients

2346

2344

91.1

87.3

Cohort

No chemotherapy, TEXT

No chemotherapy, SOFT

Chemotherapy, TEXT

Prior chemotherapy, SOFT

526

470

806

544

527

473

801

543

96.1

95.8

89.8

84.3

93.0

93.1

84.680.6Lymph Node Status

NegativePositive1362984

1350994

95.1

85.6

91.6

81.4

Exemestane With Ovarian Function Suppression Improved DFS

Pagani

O, et al. ASCO 2014. Abstract LBA1.

Reprinted with permission.

100

80

60

40

20

0

0

Percent Alive and Disease Free

1

2

3

4

5

6

Yrs Since Randomization

Median follow-up: 5.7 yrs

Difference 3.8% at 5 yrs

Exemestane + OFS (n = 2346)

Tamoxifen + OFS (n = 2344)

E + OFS

T + OFS

Events

216

298

HR

0.72

95% CI

0.60-0.85

P

Value

.0002

5-yr DFS

91.1%

87.3%

.25

.50

.72

1.0

2.0

4.0

Favors E + OFS

Favors T + OFSSlide25

Joint Analysis of TEXT and SOFT

Outcome

HR (95% CI)

p value

DFS

0.72 (0.60-0.85

0.0002

BCFI

0.66 (0.55-0.80)

<0.0001

DDFI

0.78 (0.62-0.97)

0.02

OS

1.14 (0.86-1.51)0.37Exemestane + OFS vs Tamoxifen + OFSMedian Follow-up of 5.7 years

Pagani et al. NEJM 2014Slide26

TEXT and SOFT: Selected Adverse Events

CTCAE

v3.0,

%

Exemestane + OFS

(N = 2318)

Tamoxifen + OFS (N = 2325)

Grades 1-4

Grades

3/4

Grades 1-4

Grades

3/4

Depression

50

3.8

50

4.4

Musculoskeletal

89

11

76

5.2

Osteoporosis

(%

T

score < -2.5)

39 (13)0.425 (6)0.3

Fracture

6.81.35.2

0.8Hypertension236.5

227.3Cardiac ischemia/infarction0.70.3

0.30.1Thrombosis/embolism1.00.8

2.21.9CNS ischemia0.7

0.30.30.1CNS bleeding

0.6< 0.10.90.1Hot flushes/flashes

92109312

Sweating55NR59 NR

Vaginal dryness

52

NR

47

NR

Libido decrease

45

NR

41

NR

Dyspareunia

31

2.3

26

1.4

Urinary incontinence

13

0.3

18

0.3

Pagani

O, et al. ASCO 2014. Abstract LBA1.

Reprinted with permission.Slide27
Slide28

Final Analysis of ABCSG 12

HR vs Tam

1.13 (0.88-1.45)

p=0.33

HR vs Tam

1.63 (1.05-2.52

p=0.03

DFS

OS

Gnant, et al Ann Oncol 2014Slide29

Adjuvant Endocrine Therapy for Premenopausal Women

Several evidence-based choices now available:Tamoxifen x 5-10 yrTamoxifen x 5 yr to AI x 5 yr (MA-17)OFS + Tamoxifen

OFS + AI

Davidson N, Commentary SABCS 2014Slide30

Adjuvant Endocrine Therapy for Premenopausal Women

Tamoxifen alone x 5-10 years sufficient for low riskConsider use of OFS + Tam or OFS + AI for higher risk womenChemotherapy recipientsMultiple positive nodes

Age < 35

Optimal duration of OFS-based therapy uncertain

Long-term follow-up for both benefit and toxicity

Davidson N, Commentary SABCS 2014Slide31

Rugo

H. Commentary at 2014 SABCSSlide32

Challenges in Optimal Endocrine Therapy

Predictive markers beyond ER, PRUnderstanding pathways of resistance and when they come into playOptimizing the host environment – BMI?Monitoring the long-term benefit and toxicityCompliance and adherence of the patient (and their health care provider)

Davidson N, SABCS 2014 CommentarySlide33

Obesity in Breast Cancer

Early Breast Cancer Trialists’ Collaborative Group collected data on 80,000 patients with early breast cancer to analyze independent effects of BMI on patient outcomeObesity independently associated with BC-related mortality in premenopausal pts

with ER+ BC

In premenopausal obese (BMI ≥ 30) vs normal-weight women with ER+ disease (N = 20,000): 10-yr BC-relate mortality: 21.5% vs 16.6% (RR = 1.34; 95% CI: 1.22-1.47; 2P < .00001)

Little effect in premenopausal women with ER-negative disease or in postmenopausal women

Postmenopausal ER+ (N = 40,000): RR = 1.06 (95% CI: 0.99-1.14)

Pre- or postmenopausal ER-negative (N = 20,000): RR: 1.00 (95% CI: 0.93-1.08)

Pan H, et al. ASCO 2014. Abstract 503.Slide34
Slide35
Slide36

BMI: Impact on Efficacy of Endocrine Therapy in ABCSG-12

Pfeiler

, et al. JCO 2011Slide37

BMI: Impact on Efficacy of Endocrine Therapy in ABCSG-12

Pfeiler

, et al. JCO 2011Slide38

BMI: Impact on Efficacy of Endocrine Therapy in ABCSG-12

ConclusionsThese data are hypothesis generating secondary to the retrospective analysis.However, it does suggest that BMI influences the efficacy of OFS+ Anastrozole in premenopausal women when compared to tamoxifen +OFS.

Because over 1/3 of premenopausal women who develop breast cancer are overweight or obese, consideration should be given regarding selection of endocrine therapy.

Pfeiler

, et al. JCO 2011Slide39

Conclusions

Very little practice-changing data in the use of adjuvant chemotherapy.SOFT may present a new paradigm for young high-risk women with ER (+) early breast cancer.The role of BMI may need to be considered when selecting endocrine therapy for our patients.