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

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Beyond the Guidelines: Clinical Investigators Provide Their Perspectives on Current Strategies and Ongoing Research in the Management of Breast Cancer Wednesday, December 11, 2013 7:30 PM 9:30 PM San Antonio, Texas Moderator Neil Love, MD Lisa A Carey, MD Clifford Hudis, MD Hope S Rugo, MD Faculty George W Sledge Jr, MD Sunil Verma, MD, MSEd

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: 40 T: 1.5 cm N: 1+ AC-TH 16 TCH 9 Other 1

Adjuvant Rx: ER-neg, HER2+ Age: 40 T: 1.5 cm N: 0 TCH 12 Pac/Tras 7 AC-TH 6 Other 1

Rx: ER-neg, HER2+ Age: 40 T: 0.8 cm N: 0 Pac/Tras 12 TCH 9 AC-TH 3 Doc/Cyc/Tras 2

Neoadjuvant Rx: ER-neg, HER2+ Age: 40 T: 4 cm Tumor shrinkage needed for BCS Anti-HER2 Treatment (with Chemo) Trastuzumab/ pertuzumab 24 Trastuzumab 2 Choice of Chemotherapy Taxane and anthracycline 16 Taxane 10

Neoadjuvant Rx: ER-neg, HER2+ Age: 40 T: 2 cm Anti-HER2 Treatment Trastuzumab/ pertuzumab/ chemo 21 Trastuzumab/ chemo 5 Choice of Chemotherapy Taxane 15 Taxane and anthracycline 10 Other* 1 * N-: taxane-based or N+: taxane + anthracycline-based

Adjuvant Rx: ER-neg, HER2+ Age: 75 T: 1.5 cm N: 1+ TCH 13 Pac/Tras 6 AC-TH 4 Doc/Cyc/Tras 2 Other 1

Adjuvant Rx: ER-neg, HER2+ Age: 75 T: 1.5 cm N: 0 Pac/Tras 13 TCH 9 Doc/Cyc/Tras Other* 2 2 * Dose-dense AC-TH; no systemic therapy

Adjuvant Rx: ER-neg, HER2+ Age: 75 T: 0.8 cm N: 0 Pac/Tras 18 None 3 TCH 2 Other 3

Module 2

Would you order 21-gene Recurrence Score (RS)? (ER+, HER2-neg) Age: 40 T: 1.5 cm N: 0 Yes 23 No 3

Would you order 21-gene RS? (ER+, HER2-neg) Age: 40 T: 1.5 cm N: 1+ Yes 9 No 17

Would you order 21-gene RS? (ER+, HER2-neg) Age: 75 T: 1.5 cm N: 0 Yes 11 No 15

Would you order 21-gene RS? (ER+, HER2-neg) Age: 75 T: 1.5 cm N: 1+ Yes 14 No 12

Do the following assays predict benefit from adjuvant chemotherapy? Oncotype DX 25 MammaPrint 9 IHC4 5 PAM50 4 EPclin 1

60 yo patient 4.0-cm, ER+++, HER2-neg IDC requiring tumor shrinkage for BCS 21-gene RS? It s a good idea 11 It s not a good idea 9 Other 6

Continuation of endocrine treatment at 5 years Age: 40 Original tumor: 1.5 cm, node-neg Rx: Tamoxifen Continue tamoxifen 17 Stop tamoxifen (no further ET) 6 Other 3

Continuation of endocrine treatment at 5 years Age: 40 Original tumor T: 1.5 cm; N: 2+ Rx: Tamoxifen Continue tamoxifen 23 Switch to OS/A + AI 2 Stop tamoxifen (no further ET) 1

Continuation of endocrine treatment at 5 years Age: 75 Original tumor T: 1.5 cm; N: 0 Rx: AI Stop anastrozole (no further ET) 24 Continue anastrozole 2

Continuation of endocrine treatment at 5 years Age: 75 Original tumor T: 1.5 cm; N: 2+ Rx: AI Continue anastrozole 15 Stop anastrozole (no further ET) 11

Module 3

ER-neg, HER2+ mbc (no prior systemic Rx) Usual 1 st -line Rx Trastuzumab/ pertuzumab/ taxane 25 Trastuzumab/ taxane 1 Choice of Taxane Paclitaxel 17 Docetaxel 8 Nab paclitaxel 1

ER-neg, HER2+ mbc (adj TCH 12 mo ago) Usual 1 st -line Rx Trastuzumab/ pertuzumab/ taxane 21 T-DM1 4 Other* 1 Choice of Taxane Paclitaxel 14 Docetaxel 5 Nab paclitaxel 2 * Trastuzumab/pertuzumab/eribulin

ER-neg, HER2+ mbc Usual 2 nd -line Rx T-DM1 22 Trastuzumab/ lapatinib Capecitabine/ lapatinib 1 1 Other 2

ER+, HER2+ mbc Age 45, premenopausal Minimally symptomatic, liver mets Trastuzumab + pertuzumab + taxane 24 Other* 2 * ET + trastuzumab; trastuzumab + pertuzumab + ET

ER+, HER2+ mbc Age 45, premenopausal Asymptomatic Low disease burden bone mets ET + Tras 10 ET 5 Tras/Pert/ taxane 7 Other* 4 * Trastuzumab/pertuzumab/ET x 2; trastuzumab + taxane; ET + lapatinib + trastuzumab

ER+, HER2+ Age 75, postmenopausal Asymptomatic Low disease burden bone mets ET + Tras 14 ET 6 Tras + Pert + ET Other* 3 3 * Nab paclitaxel + trastuzumab + pertuzumab; ET + trastuzumab + lapatinib; letrozole + lapatinib

ER+, HER2+ Age 75, postmenopausal Somewhat symptomatic, liver mets Tras+ Pert + taxane 17 ET + Tras 6 Other* 3 * ET; nab paclitaxel + trastuzumab + pertuzumab; letrozole + lapatinib

T-DM1 with pertuzumab outside of a trial? No 25 Yes 1

Module 4

60 yo woman ER-neg, HER2-neg IDC Postlumpectomy local recurrence 2 years after AC à T None 4 TC or CMF 13 Gemcitabine + platinum 3 Capecitabine 2 Other chemo 4

60 yo woman ER+, HER2+ IDC Postlumpectomy local recurrence while on anastrozole 2 years after AC à TH ET + anti-her2 8 ET alone 8 Chemo + anti-her2 plus or followed by ET 6 Chemo + anti-her2 4

60 yo woman ER-neg, HER2+ IDC Postlumpectomy local recurrence 2 years after AC à TH None 5 TCH THP 6 6 Other chemo + trastuzumab Trastuzumab ± lapatinib 2 3 Other 4

ER/PR/HER2-neg mbc (BRCA+) Do PARP inhibitors demonstrate efficacy? Yes, both w and w/o chemo 14 Yes, without chemo 7 I don t know 5

ER/PR/HER2-neg mbc (BRCA-neg) Do PARP inhibitors demonstrate efficacy? No 13 I don t know 12 Yes, with chemo 1

ER/PR/HER2-neg mbc Relative efficacy of capecitabine versus eribulin? Eribulin is more efficacious 11 About the same 10 I don t know 4 Capecitabine is more efficacious 1

ER+, HER2-neg mbc resistant to ET Efficacy of capecitabine versus eribulin? About the same 18 Capecitabine more efficacious 3 Eribulin more efficacious 2 I don t know 3

Consider the last patient in your practice who died of breast cancer How long did the patient live with (triple-negative) mbc? <12 months 5 12-24 months 19 >24 months 2 Median = 17 months

Was she referred for hospice care? 15 Weeks 10 5 1 5 10 15 20 Patient # 25 Median duration was 4 weeks.

Time between last dose of chemotherapy for triplenegative mbc and patient s death? 25 20 Weeks 15 10 5 1 5 10 15 20 25 Patient # Median = 8 weeks

Most common systemic agents administered Eribulin 21 Platinum 21 Capecitabine 19 Gemcitabine 18 Taxane 17

Module 5

ER+, HER2-neg mbc Age 65, postmenopausal Asymptomatic Low disease burden bone mets After 4 years adjuvant anastrozole Fulvestrant 14 Exemestane/ everolimus 8 Other* 4 * Tamoxifen x 2; exemestane; fulvestrant + AI

ER+, HER2-neg mbc Age 65, postmenopausal Asymptomatic Low disease burden bone and liver mets After 4 years adjuvant anastrozole Fulvestrant 12 Exemestane/ everolimus 11 Tamoxifen 2 Other 1

Preemptive antimucositis measures in patients receiving everolimus? Yes 15 No 11

ER+, HER2-neg mbc Age 65, postmenopausal Asymptomatic Low disease burden bone mets After 1 year adjuvant anastrozole Fulvestrant 13 Exemestane/ everolimus 9 Tamoxifen Other* 2 2 * Exemestane; fulvestrant + AI

ER+, HER2-neg mbc Age 65, postmenopausal Asymptomatic Low disease burden bone and liver mets After 1 year adjuvant anastrozole Exemestane/ everolimus 12 Fulvestrant 11 Other* 3 * Fulvestrant + AI; capecitabine; tamoxifen

ER+, HER2-neg mbc Relapse after 4 years of nonsteroidal AI Efficacy of high-dose fulvestrant versus everolimus/ exemestane? I don t know 11 Exemestane/ everolimus more efficacious 10 About the same 5