Beyond the Guidelines: Clinical Investigators Provide Their Perspectives on Current Strategies and Ongoing Research in the Management of Breast Cancer

Beyond the Guidelines: Clinical Investigators Provide Their Perspectives on Current Strategies and Ongoing Research in

the Management of Breast Cancer

Wednesday, December 11, 20137:30 PM – 9:30 PMSan Antonio, Texas

Faculty Lisa A Carey, MDClifford Hudis, MDHope S Rugo, MD

George W Sledge Jr, MDSunil Verma, MD, MSEd

ModeratorNeil Love, MD

Survey Faculty

Kathy S Albain, MD

Kimberly L Blackwell, MD

Howard A Burris III, MD

Harold J Burstein, MD, PhD

Lisa A Carey, MD

Rowan T Chlebowski, MD, PhD

Javier Cortes, MD, PhD

Kevin R Fox, MD

Julie R Gralow, MD

Daniel F Hayes, MD

Clifford Hudis, MD

Sara A Hurvitz, MD

Ian E Krop, MD, PhD

Hannah M Linden, MD

John Mackey, MD

Kathy D Miller, MD

Hyman B Muss, MD

Ruth O’Regan, MD

Joyce O’Shaughnessy, MD

Hope S Rugo, MD

Andrew D Seidman, MD

George W Sledge Jr, MD

Ian E Smith, MD

Joseph A Sparano, MD

Sunil Verma, MD, MSEd

Eric P Winer, MD

Module 1

Adjuvant Rx: ER-neg, HER2+Age: 40T: 1.5 cmN: 1+

AC-TH AC-TH 1616

99

11

TCH TCH

OtherOther

Adjuvant Rx: ER-neg, HER2+Age: 40T: 1.5 cmN: 0

TCH TCH 1212

77

66

11

Pac/TrasPac/Tras

AC-TH AC-TH

Other Other

Rx: ER-neg, HER2+Age: 40T: 0.8 cmN: 0

Pac/TrasPac/Tras 1212

99

33

22

TCH TCH

AC-TH AC-TH

Doc/Cyc/TrasDoc/Cyc/Tras

Neoadjuvant Rx: ER-neg, HER2+Age: 40T: 4 cmTumor shrinkage needed for BCS

Trastuzumab/pertuzumab

Trastuzumab/pertuzumab

2424

22TrastuzumabTrastuzumab

Anti-HER2 Treatment (with Chemo)Anti-HER2 Treatment (with Chemo)

Choice of ChemotherapyChoice of Chemotherapy

Taxane and anthracycline


1616

1010TaxaneTaxane

Neoadjuvant Rx: ER-neg, HER2+Age: 40T: 2 cm

Trastuzumab/pertuzumab/

chemo


chemo

2121

55Trastuzumab/

chemo Trastuzumab/

chemo

Anti-HER2 TreatmentAnti-HER2 Treatment

Choice of ChemotherapyChoice of Chemotherapy

Taxane Taxane 1515

1010

11



Other* Other*

* N-: taxane-based or N+: taxane + anthracycline-based* N-: taxane-based or N+: taxane + anthracycline-based

Adjuvant Rx: ER-neg, HER2+Age: 75T: 1.5 cmN: 1+

TCH TCH 1313

66

44

22

Pac/TrasPac/Tras

AC-TH AC-TH


OtherOther 11


Pac/TrasPac/Tras 1313

99

22

22

TCH TCH


Other* Other*

*Dose-dense AC-TH; no systemic therapy*Dose-dense AC-TH; no systemic therapy


Pac/TrasPac/Tras1818

33

22

NoneNone

33Other Other

TCH TCH

Module 2

Would you order 21-gene Recurrence Score® (RS)? (ER+, HER2-neg)Age: 40T: 1.5 cm N: 0

YesYes 2323

33NoNo

Would you order 21-gene RS? (ER+, HER2-neg)Age: 40T: 1.5 cm N: 1+

YesYes 99

1717NoNo

Would you order 21-gene RS? (ER+, HER2-neg)Age: 75T: 1.5 cm N: 0

YesYes 1111

1515NoNo

Would you order 21-gene RS? (ER+, HER2-neg)Age: 75T: 1.5 cm N: 1+

YesYes 1414

1212NoNo

Do the following assays predict benefit from adjuvant chemotherapy?

Oncotype DX®Oncotype DX® 2525

99

55

44

11

MammaPrint®MammaPrint®

IHC4IHC4

PAM50 PAM50

EPclinEPclin

60 yo patient4.0-cm, ER+++, HER2-neg IDC requiring tumor shrinkage for BCS

21-gene RS?

It’s a good idea It’s a good idea 1111

99

66

It’s not a good ideaIt’s not a

good idea

OtherOther

Continuation of endocrine treatment at 5 yearsAge: 40 Original tumor: 1.5 cm, node-negRx: Tamoxifen

Continue tamoxifen

Continue tamoxifen

1717

66

33

Stop tamoxifen (no further ET) Stop tamoxifen (no further ET)

OtherOther

Continuation of endocrine treatment at 5 yearsAge: 40 Original tumor T: 1.5 cm; N: 2+Rx: Tamoxifen

Continue tamoxifen

Continue tamoxifen

2323

22

11

Switch to OS/A + AI Switch to OS/A + AI

Stop tamoxifen (no further ET) Stop tamoxifen (no further ET)

Continuation of endocrine treatment at 5 yearsAge: 75Original tumor T: 1.5 cm; N: 0Rx: AI

Stop anastrozole (no further ET)


2424

22Continue

anastrozole Continue

anastrozole

Continuation of endocrine treatment at 5 yearsAge: 75Original tumor T: 1.5 cm; N: 2+Rx: AI

Continue anastrozole

Continue anastrozole

1515

1111Stop anastrozole (no further ET)


Module 3

ER-neg, HER2+ mBC (no prior systemic Rx)Usual 1st-line Rx


taxane


taxane

2525

11Trastuzumab/

taxane Trastuzumab/

taxane

Choice of TaxaneChoice of Taxane

Paclitaxel Paclitaxel 1717

88Docetaxel Docetaxel

11Nab paclitaxel Nab paclitaxel

ER-neg, HER2+ mBC (adj TCH 12 mo ago)Usual 1st-line Rx


taxane


taxane

2121

Choice of TaxaneChoice of Taxane

Paclitaxel Paclitaxel 1414

55Docetaxel Docetaxel

22Nab paclitaxel Nab paclitaxel

* Trastuzumab/pertuzumab/eribulin * Trastuzumab/pertuzumab/eribulin

44

11

T-DM1 T-DM1

Other* Other*

ER-neg, HER2+ mBCUsual 2nd-line Rx

T-DM1 T-DM1 2222

11

11

Trastuzumab/lapatinib

Trastuzumab/lapatinib

Capecitabine/lapatinib

Capecitabine/lapatinib

22OtherOther

ER+, HER2+ mBCAge 45, premenopausalMinimally symptomatic, liver mets

Trastuzumab + pertuzumab +

taxane

Trastuzumab + pertuzumab +

taxane

2424

22Other* Other*

* ET + trastuzumab; trastuzumab + pertuzumab + ET* ET + trastuzumab; trastuzumab + pertuzumab + ET

ER+, HER2+ mBCAge 45, premenopausalAsymptomaticLow disease burden bone mets

ET + TrasET + Tras 1010

55

77

44

ET ET

Tras/Pert/taxane

Tras/Pert/taxane

Other* Other*

* Trastuzumab/pertuzumab/ET x 2; trastuzumab + taxane; ET + lapatinib + trastuzumab* Trastuzumab/pertuzumab/ET x 2; trastuzumab + taxane; ET + lapatinib + trastuzumab

ER+, HER2+Age 75, postmenopausalAsymptomaticLow disease burden bone mets

ET + TrasET + Tras 1414

66

33

33

ET ET

Tras + Pert + ET Tras + Pert + ET

Other* Other*

* Nab paclitaxel + trastuzumab + pertuzumab; ET + trastuzumab + lapatinib; letrozole + lapatinib * Nab paclitaxel + trastuzumab + pertuzumab; ET + trastuzumab + lapatinib; letrozole + lapatinib

ER+, HER2+Age 75, postmenopausalSomewhat symptomatic, liver mets

Tras+ Pert + taxane

Tras+ Pert + taxane

66

33

ET + TrasET + Tras

Other* Other*

*ET; nab paclitaxel + trastuzumab + pertuzumab; letrozole + lapatinib

*ET; nab paclitaxel + trastuzumab + pertuzumab; letrozole + lapatinib

1717

T-DM1 with pertuzumab outside of a trial?

NoNo 2525

11YesYes

Module 4

60 yo womanER-neg, HER2-neg IDCPostlumpectomy local recurrence 2 years after AC T

None None 44

1313

33

22

44

TC or CMF TC or CMF

Gemcitabine + platinum

Gemcitabine + platinum

CapecitabineCapecitabine

Other chemoOther chemo

60 yo womanER+, HER2+ IDCPostlumpectomy local recurrence while on anastrozole 2 years after AC TH

ET + anti-HER2 ET + anti-HER2 88

88

66

44

ET alone ET alone

Chemo + anti-HER2 plus or

followed by ET

Chemo + anti-HER2 plus or

followed by ET

Chemo + anti-HER2

Chemo + anti-HER2

60 yo womanER-neg, HER2+ IDCPostlumpectomy local recurrence 2 years after AC TH

None None 55

66

66

33

22

TCH TCH

THPTHP

Other chemo + trastuzumab

Other chemo + trastuzumab

Trastuzumab ± lapatinib

Trastuzumab ± lapatinib

44Other Other

ER/PR/HER2-neg mBC (BRCA+) Do PARP inhibitors demonstrate efficacy?

Yes, both w and w/o chemo

Yes, both w and w/o chemo 1414

77

55

Yes, without chemo

Yes, without chemo

I don’t know I don’t know

ER/PR/HER2-neg mBC (BRCA-neg) Do PARP inhibitors demonstrate efficacy?

NoNo 1313

1212

11


Yes, with chemo Yes, with chemo

ER/PR/HER2-neg mBCRelative efficacy of capecitabine versus eribulin?

Eribulin is more efficacious

Eribulin is more efficacious 1111

1010

44

11

About the same About the same


Capecitabine is more efficacious

Capecitabine is more efficacious

ER+, HER2-neg mBC resistant to ETEfficacy of capecitabine versus eribulin?

About the sameAbout the same 1818

33

22

33

Capecitabine more efficacious

Capecitabine more efficacious

Eribulin more efficacious

Eribulin more efficacious

I don’t knowI don’t know

Consider the last patient in your practice who died of breast cancerHow long did the patient live with (triple-negative) mBC?

<12 months<12 months 55

1919

22

12-24 months 12-24 months

>24 months >24 months

Median = 17 monthsMedian = 17 months

Was she referred for hospice care?

Median duration was 4 weeks.Median duration was 4 weeks.

Wee

ksW

eeks

1515

1010

55

11 55 1010 1515 2020

Patient #Patient #

2525

Time between last dose of chemotherapy for triple-negative mBC and patient’s death?

2525

Patient #Patient #Median = 8 weeksMedian = 8 weeks

Wee

ksW

eeks

2020

1515

1010

55

11 55 1010 1515 2020 2525

Most common systemic agents administered

Eribulin Eribulin 2121

2121

1919

1818

1717

Platinum Platinum

Capecitabine Capecitabine

Gemcitabine Gemcitabine

Taxane Taxane

Module 5

ER+, HER2-neg mBCAge 65, postmenopausalAsymptomaticLow disease burden bone metsAfter 4 years adjuvant anastrozole

Fulvestrant Fulvestrant 1414

88

44

Exemestane/everolimus


Other*Other*

*Tamoxifen x 2; exemestane; fulvestrant + AI*Tamoxifen x 2; exemestane; fulvestrant + AI

ER+, HER2-neg mBCAge 65, postmenopausalAsymptomaticLow disease burden bone and liver metsAfter 4 years adjuvant anastrozole

FulvestrantFulvestrant 1212

1111

22

11



TamoxifenTamoxifen

OtherOther

Preemptive antimucositis measures in patients receiving everolimus?

YesYes 1515

1111NoNo

ER+, HER2-neg mBCAge 65, postmenopausalAsymptomaticLow disease burden bone metsAfter 1 year adjuvant anastrozole

*Exemestane; fulvestrant + AI*Exemestane; fulvestrant + AI

Fulvestrant Fulvestrant 1313

99

22

22



TamoxifenTamoxifen

Other*Other*

ER+, HER2-neg mBCAge 65, postmenopausalAsymptomaticLow disease burden bone and liver metsAfter 1 year adjuvant anastrozole


Exemestane/everolimus 1212

1111

33

Fulvestrant Fulvestrant

Other*Other*

*Fulvestrant + AI; capecitabine; tamoxifen*Fulvestrant + AI; capecitabine; tamoxifen

ER+, HER2-neg mBCRelapse after 4 years of nonsteroidal AIEfficacy of high-dose fulvestrant versus everolimus/exemestane?

I don’t knowI don’t know 1111

1010

55

Exemestane/everolimus more

efficacious

Exemestane/everolimus more

efficacious

About the same About the same

Documents

Beyond the Guidelines: Clinical Investigators Provide Their Perspectives on Current Strategies and Ongoing Research in the Management of Breast Cancer