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Meet The Professors
Oncologist and Nurse Investigators
Consult on Challenging Patient
Cases in Breast Cancer
Friday, November 12, 2010
6:00 AM – 7:30 AM
Peabody Orlando Hotel
Moderator
Neil Love, MD
Faculty
Kimberly L Blackwell, MD
Una Hopkins, MSN, FNP-BC
Georgia Litsas, MSN, ANP-BC, AOCNP
Ruth O’Regan, MD
Copyright © 2011 Research To Practice. All rights reserved.
Agenda
Module 1 Treatment of HER2-Positive Breast Cancer in the Adjuvant
and Metastatic Settings: Ms Litsas
Module 2 Sequential Approaches for Patients with Advanced
ER-Positive, HER2-Negative Disease: Ms Hopkins
Module 3 Treatment Options for Patients with Triple-Negative
Breast Cancer (TNBC): Ms Litsas
Module 4 Evolving Clinical Research Strategies for Patients with
Advanced ER-Positive, HER2-Negative Breast Cancer:
Ms Hopkins
Panel Discussion and Response to Audience Questions
Copyright © 2011 Research To Practice. All rights reserved.
Copyright © 2011 Research To Practice. All rights reserved.
National Patterns of Care Study in
Breast Cancer
• Launched October 2010
• 100 US-based community oncologists surveyed
• Proportion of patients/office visits with
breast cancer: 30% (median)
• New patients with breast cancer seen per
month: 15 (median)
Patterns of Care in Breast Cancer, Research To Practice 2010.
Copyright © 2011 Research To Practice. All rights reserved.
Copyright © 2011 Research To Practice. All rights reserved.
Copyright © 2011 Research To Practice. All rights reserved.
Meet The Professors
Oncologist and Nurse Investigators
Consult on Challenging Patient
Cases in Breast Cancer
Friday, November 12, 2010
6:00 AM – 7:30 AM
Peabody Orlando Hotel
Moderator
Neil Love, MD
Faculty
Kimberly L Blackwell, MD
Una Hopkins, MSN, FNP-BC
Georgia Litsas, MSN, ANP-BC, AOCNP
Ruth O’Regan, MD
Copyright © 2011 Research To Practice. All rights reserved.
Case 1 (Ms Litsas)
A 64-year-old woman was diagnosed in
2003 with an ER-negative, HER2-positive,
node-positive invasive ductal carcinoma
(IDC) and received adjuvant
chemotherapy. In 2006, metastases were
diagnosed and since then the patient has
received a series of regimens, including
anti-HER2 agents and chemotherapy,
both on and off protocol.
Copyright © 2011 Research To Practice. All rights reserved.
Copyright © 2011 Research To Practice. All rights reserved.
In addition to endocrine treatment what do you
generally recommend as adjuvant therapy for a
60-year-old woman with an ER-positive,
HER2-positive tumor and one positive node?
TCH (docetaxel, carboplatin,
trastuzumab)
55%
AC-TH (anthracycline +
cyclophosphamide + taxane +
trastuzumab)
38%
TC (docetaxel +
cyclophosphamide) +
trastuzumab
Paclitaxel + trastuzumab
5%
2%
Patterns of Care Survey of US-Based Practicing Oncologists (n = 99)
Copyright © 2011 Research To Practice. All rights reserved.
Copyright © 2011 Research To Practice. All rights reserved.
In addition to endocrine treatment what do you
generally recommend as adjuvant therapy for a
75-year-old woman with an ER-positive,
HER2-positive tumor and one positive node?
TCH (docetaxel, carboplatin,
trastuzumab)
56%
TC (docetaxel +
cyclophosphamide) +
trastuzumab
18%
AC-TH (anthracycline +
cyclophosphamide + taxane +
trastuzumab)
9%
Paclitaxel + trastuzumab
9%
Other
8%
Patterns of Care Survey of US-Based Practicing Oncologists (n = 99)
Copyright © 2011 Research To Practice. All rights reserved.
Copyright © 2011 Research To Practice. All rights reserved.
In addition to endocrine treatment what do you
generally recommend as adjuvant therapy for a
60-year-old woman with a 0.8-cm, node-negative,
ER-positive, HER2-positive tumor?
TCH (docetaxel
+ carboplatin + trastuzumab)
56%
TC (docetaxel +
cyclophosphamide) + trastuzumab
14%
AC-TH (anthracycline +
cyclophosphamide
+ taxane + trastuzumab)
8%
7%
Trastuzumab alone
Paclitaxel + trastuzumab
None
4%
6%
Patterns of Care Survey of US-Based Practicing Oncologists (n = 99)
Copyright © 2011 Research To Practice. All rights reserved.
Copyright © 2011 Research To Practice. All rights reserved.
In general what treatment do you recommend for a 60-year-old
patient with an ER-positive, HER2-positive tumor who received
adjuvant chemotherapy/trastuzumab and endocrine treatment
but develops disease relapse six months after finishing
adjuvant trastuzumab?
36%
Lapatinib + chemotherapy
21%
Lapatinib + endocrine therapy
16%
Trastuzumab + chemotherapy
Trastuzumab + endocrine
therapy
13%
Lapatinib alone
5%
Lapatinib + trastuzumab +
chemotherapy
5%
Other
4%
Patterns of Care Survey of US-Based Practicing Oncologists (n = 99)
Copyright © 2011 Research To Practice. All rights reserved.
Copyright © 2011 Research To Practice. All rights reserved.
In general what treatment do you recommend for a 60-year-old
patient with an ER-positive, HER2-positive tumor who received
adjuvant chemotherapy/trastuzumab and endocrine treatment
but develops disease relapse 18 months after finishing
adjuvant trastuzumab?
40%
Trastuzumab + chemotherapy
Trastuzumab + endocrine
therapy
28%
15%
Lapatinib + chemotherapy
6%
Lapatinib + endocrine therapy
Trastuzumab alone
3%
Lapatinib alone
3%
Other
5%
Patterns of Care Survey of US-Based Practicing Oncologists (n = 99)
Copyright © 2011 Research To Practice. All rights reserved.
Breast Cancer Subtypes
(Luminal B subtype)
(TNBC aka
basal-like subtype)
(HER2+ subtype)
(Luminal A subtype)
(Assumptions: ER+ 75%a; HER2+ 20%b)
aLi
CI et al. J Clin Oncol 2003;21:28-34.
H et al. JAMA 2004;29(16):1972-77.
bYaziji
Copyright © 2011 Research To Practice. All rights reserved.
Signal Transduction by the HER Family
Promotes Proliferation, Survival and Invasiveness
Receptor specific
ligands
HER2
HER2
HER4
HER1, HER2,
HER3, or HER4
HER3
VEGF
HER1
(EGFR)
Plasma
membrane
P
PI3K
Tyrosine kinase
domains
Akt
SOS
P
RAS
MAP
K
Cytoplasm
P
P
RAF
MEK
Cell proliferation
Cell survival
Cell mobility and invasiveness
Nucleus
Copyright
© 2011 Research To Practice. All rights reserved.
Transcription
20
Ongoing Adjuvant Phase III Trials for Patients
with HER2-Positive Early BC
Protocol ID: ALTTO; Accrual: 8,000
Trastuzumab q3wk x 52 wk
R
Lapatinib daily x 52 wk
Trastuzumab qwk x 12  6-wk washout  lapatinib daily x 34 wk
Lapatinib daily + trastuzumab q3wk x 52 wk
Protocol ID: BETH; Accrual: 3,500
R
TCH* or (TH  FEC†)  H to complete 1 year
TCHB* or (THB  FEC†)  HB to complete 1 year
H = trastuzumab; L = lapatinib; T = docetaxel; C = carboplatin; F = 5-FU; E = epirubicin;
C† = cyclophosphamide; B = bevacizumab
* Chemotherapy used by NSABP/CIRG investigators (Cohort 1)
† Chemotherapy used by independent investigators (Cohort 2)
NCI Physician Data Query, November 2010;
www.breastinternationalgroup.org; www.alttotrials.com.
Copyright © 2011 Research To Practice. All rights reserved.
Blackwell KL et al. J Clin Oncol 2010;28(7):1124-30.
Copyright © 2011 Research To Practice. All rights reserved.
Lapatinib (L) with or without Trastuzumab (T) for
Heavily Pretreated mBC Following Disease
Progression on T-Containing Therapy
Parameter
Median progression-free
survival (PFS)
Median overall survival
(OS)
Clinical benefit rate
Clinical benefit rate
L
(n = 145)
L+T
(n = 146)
Hazard
Ratio
p-value
8.1 wk
12.0 wk
0.73
0.008
39.0 wk
51.6 wk
0.75
0.106
12.4%
12.4%
24.7%
24.7%
Blackwell KL et al. J Clin Oncol 2010;28(7):1124-30.
--
—
0.01
0.01
Copyright © 2011 Research To Practice. All rights reserved.
What patient education information do you
consider essential for a patient with breast
cancer about to begin treatment with….
lapatinib- and/or trastuzumab-based therapy
Copyright © 2011 Research To Practice. All rights reserved.
Efficacy and Safety of Trastuzumab-DM1
vs Trastuzumab Plus Docetaxel in HER2Positive Metastatic Breast Cancer
Patients with No Prior Chemotherapy for
Metastatic Disease: Preliminary Results
of a Randomized, Multicenter, OpenLabel Phase 2 Study (TDM4450G)
Perez EA et al.
Proc ESMO 2010;Abstract LBA3.
Copyright © 2011 Research To Practice. All rights reserved.
T-DM1 versus Trastuzumab (T) + Docetaxel (D) in
HER2-Positive mBC with No Prior Chemotherapy
for mBC
T-DM1
(n = 67)
T+D
(n = 70)
47.8%
41.4%
37.3%
75.0%
Efficacy Summary*
Overall response rate (ORR)
Safety Summary
Grade ≥ 3 adverse event (AE)†
†Most
common AEs, any grade, T+D: Alopecia: 66.2%, neutropenia: 57.4%,
diarrhea: 45.6% — 1.5%, 7.5% and 10.4% in pts receiving T-DM1.
†Most
common AEs, any grade, T-DM1: Nausea: 47.8%, fatigue: 46.3%,
pyrexia: 35.8% — 39.7%, 46.2% and 20.6% in pts receiving T+D.
Perez AE et al. Proc ESMO 2010;Abstract LBA3.
Copyright © 2011 Research To Practice. All rights reserved.
Meet The Professors
Oncologist and Nurse Investigators
Consult on Challenging Patient
Cases in Breast Cancer
Friday, November 12, 2010
6:00 AM – 7:30 AM
Peabody Orlando Hotel
Moderator
Neil Love, MD
Faculty
Kimberly L Blackwell, MD
Una Hopkins, MSN, FNP-BC
Georgia Litsas, MSN, ANP-BC, AOCNP
Ruth O’Regan, MD
Copyright © 2011 Research To Practice. All rights reserved.
Case 2 (Ms Hopkins)
A 58-year-old woman was diagnosed in
1992 with an ER-positive, HER2-negative,
node-positive IDC and received CMF
followed by five years of adjuvant
tamoxifen. In 2001 metastases were
diagnosed and the patient received
several endocrine agents in sequence
followed by a sequence of single agents
alone or with bevacizumab.
Copyright © 2011 Research To Practice. All rights reserved.
Copyright © 2011 Research To Practice. All rights reserved.
Do you generally obtain biopsies for patients who
develop metastatic disease after receiving adjuvant
chemotherapy for breast cancer?
74%
Yes
56%
18%
It’s optional but
not necessary
No
60 years
30%
75 years
8%
14%
Patterns of Care Survey of US-Based Practicing Oncologists (n = 99)
Copyright © 2011 Research To Practice. All rights reserved.
Breast Cancer Subtypes
(Luminal B subtype)
(TNBC aka
basal-like subtype)
(HER2+ subtype)
(Luminal A subtype)
(Assumptions: ER+ 75%a; HER2+ 20%b)
aLi
CI et al. J Clin Oncol 2003;21:28-34.
H et al. JAMA 2004;29(16):1972-77.
bYaziji
Copyright © 2011 Research To Practice. All rights reserved.
Copyright © 2011 Research To Practice. All rights reserved.
In general what endocrine treatment do you
recommend for a postmenopausal woman who
develops metastases?
Fulvestrant
47%
Exemestane
Letrozole
Tamoxifen
27%
14%
12%
Patterns of Care Survey of US-Based Practicing Oncologists (n = 99)
Copyright © 2011 Research To Practice. All rights reserved.
What patient education information do you
consider essential for a patient with breast
cancer about to begin treatment with….
fulvestrant
Copyright © 2011 Research To Practice. All rights reserved.
What patient education information do you
consider essential for a patient with breast
cancer about to begin treatment with….
fulvestrant
Copyright © 2011 Research To Practice. All rights reserved.
Di Leo A et al. J Clin Oncol 2010;28(30):4594-600.
Copyright © 2011 Research To Practice. All rights reserved.
Proportion of Patients Alive
Proportion of Patients Progression Free
CONFIRM Trial Results
Time (months)
Objective Response and Clinical
Benefit
Time (months)
Fulvestrant 500 mg
(n=362)
Fulvestrant 250 mg (n=374)
Objective response
9.1%
10.2%
Complete response
1.1%
0.3%
Clinical benefit
45.6%
39.6%
Reprinted with permission. © 2010 American Society of Clinical Oncology. All rights reserved.
Di Leo A et al. J Clin Oncol 2010;28:4594-600.
Copyright © 2011 Research To Practice. All rights reserved.
Case 2 (Ms Hopkins)
A 58-year-old woman was diagnosed in
1992 with an ER-positive, HER2-negative,
node-positive IDC and received CMF
followed by five years of adjuvant
tamoxifen. In 2001 metastases were
diagnosed and the patient received
several endocrine agents in sequence
followed by a sequence of single agents
alone or with bevacizumab.
Copyright © 2011 Research To Practice. All rights reserved.
Copyright © 2011 Research To Practice. All rights reserved.
What patient education information do you
consider essential for a patient with breast
cancer about to begin treatment with….
paclitaxel/bevacizumab
Copyright © 2011 Research To Practice. All rights reserved.
Copyright © 2011 Research To Practice. All rights reserved.
Overview of Efficacy Results from Individual Studies
E2100
Median
PFS
(months)
RIBBON-1
(Capecitabine)
AVADO
NonBV
BV
5.8
11.3
Non-BV BV1 Non-BV
7.9
8.8
5.7
RIBBON-1
(Taxane,
Anthra)
BV
NonBV
BV
8.6
8.0
9.2
Hazard
Ratio
0.48
0.62
0.69
0.64
p-value
<0.0001
0.0003
0.0002
<0.0001
Anthra = Anthracycline
1 Bevacizumab 15 mg/kg data
O’Shaughnessy J et al. Proc ASCO 2010. Abstract 1005.
Copyright © 2011 Research To Practice. All rights reserved.
O’Shaughnessy J et al. Proc ASCO 2010. Abstract 1005.
Copyright © 2011 Research To Practice. All rights reserved.
Meta-Analysis of Three Studies of Bevacizumab-Containing FirstLine Therapy in Breast Cancer: E2100, AVADO, RIBBON-1
Non-BV
(n = 1,008)
BV
(n = 1,439)
Hazard
Ratio
p-value
PFS (in
months)
6.7
9.2
0.64
<0.0001
OS (in months)
26.4
26.7
0.97
0.560
1-year survival
77%
82%

0.003
O’Shaughnessy J et al. Proc ASCO 2010. Abstract 1005.
Copyright © 2011 Research To Practice. All rights reserved.
Percent of Grade >3 Selected Adverse Events:
Pooled Population from Phase III Studies
Non-BV (n = 982)
BV (n = 1679)
Neutropenia
7.1
10.0
Sensory neuropathy
8.5
9.5
Hypertension
1.2
9.0
Febrile neutropenia
3.5
6.5
Venous thromboembolic event
3.8
2.8
0
2.3
0.3
1.6
0
<0.1
Proteinuria
Arterial thromboembolic event
RPLS
O’Shaughnessy J et al. Proc ASCO 2010. Abstract 1005.
Copyright © 2011 Research To Practice. All rights reserved.
What patient education information do you
consider essential for a patient with breast
cancer about to begin treatment with….
capecitabine
Copyright © 2011 Research To Practice. All rights reserved.
Case 3 (Ms Litsas)
A 73-year-old woman diagnosed in early
2010 with de novo metastatic TNBC
consents to participation in the CALGB40502 clinical trial of bevacizumab with
paclitaxel, nab paclitaxel or ixabepilone.
Copyright © 2011 Research To Practice. All rights reserved.
Estimated New Cancer Cases per Year in the US
Estimated New Cases
Breast
Triple-negative subset1
209,060
~31,359
Pancreas
43,140
CNS
22,020
Ovarian
21,880
Gastric
21,000
Multiple myeloma
20,180
Hodgkin lymphoma
8,490
Chronic myeloid leukemia
4,870
1 Value
estimated by multiplying the number of new breast cancer cases by reported 15%
incidence (Stead, Breast Cancer Res 2009) of TNBC.
Jemal A et al. CA Cancer J Clin 2010;60(5):277-300.
Copyright © 2011 Research To Practice. All rights reserved.
Comparison of Subgroup Analyses
of PFS from Three Phase III Studies
of Bevacizumab in Combination
with Chemotherapy in Patients
with HER2-Negative Metastatic
Breast Cancer
O’Shaughnessy J et al.
Proc SABCS 2009;Abstract 207.
Copyright © 2011 Research To Practice. All rights reserved.
Improvement in PFS for Patient Subgroups
with Addition of Bevacizumab (B) in E2100,
AVADO and RIBBON-1
Improvement in PFS (mos)
E2100
(n = 722)
AVADO*
(n = 736)
RIBBON-1†
(n = 1,237)
Overall
5.5
0.8, 0.9
2.9, 1.2
Triple-negative
5.3
0.8, 2.8
1.9, 0.3
Neoadjuvant/adjuvant taxane
7.3
4.2, 1.9
4.5, 2.4
Age ≥ 65
4.3
0.8, 0.8
2.9, 1.6
Patient Subgroup
* B 7.5 mg/kg; 15 mg/kg.
† Capecitabine/B; Taxane/anthracycline/B
O’Shaughnessy J et al. Proc SABCS 2009;Abstract 207.
Copyright © 2011 Research To Practice. All rights reserved.
Synthetic Lethality — The Principle
Chang J. TNBC 101 Research To Practice
Webinar, 2010.
Copyright © 2011 Research To Practice. All rights reserved.
Final Efficacy and Safety Results of a
Randomized Phase II Study of the PARP
Inhibitor Iniparib (BSI-201) in
Combination with Gemcitabine/
Carboplatin (G/C) in Metastatic Triple
Negative Breast Cancer (TNBC)
O’Shaughnessy J et al.
Proc ESMO 2010;Abstract LBA11.
Copyright © 2011 Research To Practice. All rights reserved.
Final Efficacy Results of the Phase II Trial
of Iniparib (BSI-201) Plus Gemcitabine/
Carboplatin for Patients with mTNBC
Gem/Carbo
(n = 62)
Iniparib/Gem/Carbo
(n = 61)
p-value*
Objective response
rate
32.3%
52.5%
0.023
Clinical benefit rate
33.9%
55.7%
0.015
Median PFS
3.6 mos
5.9 mos
0.012
Median OS
7.7 mos
12.3 mos
0.014
Clinical Variable
* Not adjusted for multiple interim analyses.
O’Shaughnessy J et al. Proc ESMO 2010;Abstract LBA11.
Copyright © 2011 Research To Practice. All rights reserved.
Meet The Professors
Oncologist and Nurse Investigators
Consult on Challenging Patient
Cases in Breast Cancer
Friday, November 12, 2010
6:00 AM – 7:30 AM
Peabody Orlando Hotel
Moderator
Neil Love, MD
Faculty
Kimberly L Blackwell, MD
Una Hopkins, MSN, FNP-BC
Georgia Litsas, MSN, ANP-BC, AOCNP
Ruth O’Regan, MD
Copyright © 2011 Research To Practice. All rights reserved.
Case 4 (Ms Hopkins)
A 61-year-old woman with de novo
metastatic ER-positive, HER2-negative
breast cancer participates for more than a
year on the CALGB-40503 clinical trial of
letrozole with or without bevacizumab.
Copyright © 2011 Research To Practice. All rights reserved.
CALGB-40503: Phase III Study of Endocrine
Therapy with or without Bevacizumab for
ER-/PR-Positive Advanced Breast Cancer
Eligibility: Inoperable locally advanced or metastatic ER-positive and/or
PR-postitive breast cancer; no prior anti-VEGF or VEGFR TKI therapy
Tamoxifen or letrozole + bevacizumab
q 21 days
R
Tamoxifen or letrozole + placebo
q 21 days
www.ClinicalTrials.gov, November 2010.
Copyright © 2011 Research To Practice. All rights reserved.
Case 4 (Ms Hopkins)
A 61-year-old woman with de novo
metastatic ER-positive, HER2-negative
breast cancer participates for more than a
year on the CALGB-40503 clinical trial of
letrozole with or without bevacizumab.
Copyright © 2011 Research To Practice. All rights reserved.
Case 2 (Ms Hopkins)
A 58-year-old woman was diagnosed in
1992 with an ER-positive, HER2-negative,
node-positive IDC and received CMF
followed by five years of adjuvant
tamoxifen. In 2001 metastases were
diagnosed and the patient received
several endocrine agents in sequence
followed by a sequence of single agents
alone or with bevacizumab.
Copyright © 2011 Research To Practice. All rights reserved.
Case 1 (Ms Litsas)
A 64-year-old woman was diagnosed in
2003 with an ER-negative, HER2-positive,
node-positive invasive ductal carcinoma
(IDC) and received adjuvant
chemotherapy. In 2006, metastases were
diagnosed and since then the patient has
received a series of regimens, including
anti-HER2 agents and chemotherapy,
both on and off protocol.
Copyright © 2011 Research To Practice. All rights reserved.
Copyright © 2011 Research To Practice. All rights reserved.
Meet The Professors
Oncologist and Nurse Investigators
Consult on Challenging Patient
Cases in Breast Cancer
Friday, November 12, 2010
6:00 AM – 7:30 AM
Peabody Orlando Hotel
Moderator
Neil Love, MD
Faculty
Kimberly L Blackwell, MD
Una Hopkins, MSN, FNP-BC
Georgia Litsas, MSN, ANP-BC, AOCNP
Ruth O’Regan, MD
Copyright © 2011 Research To Practice. All rights reserved.