SlideShare a Scribd company logo
1 of 23
Primary Systemic Therapy:
Beginning the Journey
Beth Overmoyer MD, FACP
Director, Inflammatory Breast Cancer Program
1st Annual IBC Patient Forum
Dana Farber Cancer Institute
May 13, 2017
Historical Perspective of IBC
• The historical identification of IBC is important as a reminder of the
acceptance of classic clinical criteria that differentiates the disease
from other forms of locally advanced breast cancer
• 1814 – Sir Charles Bell described a grave prognosis associated with
breast cancer when the following characteristics are present:
• “when a purple color is on the skin over the tumor accompanied
by shooting pains it is a very unpropitious beginning”
• Lee and Tannenbaum (1924) – “inflammatory breast cancer”
IBC – A Distinct Subtype of Breast Cancer
Distinct subtype of breast cancer
• Definitive or pathologic
diagnostic criteria do not
exist
• “Clinical diagnosis” fraught
with potential problems,
both underestimating and
overestimating the
diagnosis
• Seer 2004-7: 2-yr BCS
• IBC = 84%
• LABC = 91%
• 43% higher risk of breast cancer death in
IBC vs. LABC
• German study: 4.5x greater risk of
dying within 5 years
Diessner Arch Gyn Obs 2015;292:655; Anderson WF, JCO 21:2254, 2003
IBC
LABC
• 1-5% incidence in US
• Difficulty in tracking the disease due to variation in diagnostic criteria
over time
• Underestimate incidence
Clinical definition with confirmed breast cancer: Rapid onset – 3 – 6 mo
• Erythema > 1/3 breast
• Edema (peau d’orange)
• Often warm breast, pain
• Breast enlargement – often without a mass
• Highly metastatic:
35% metastasis at presentation
Clinical Presentation - IBC
Clinical Diagnosis of IBC
• Tumor emboli in dermal lymphatics without classical signs is not
considered IBC
• The presence of dermal lymphatic invasion is not necessary for
the diagnosis of IBC
“Trimodality” Therapy: Importance of pCR
Primary
Systemic Therapy
Mastectomy +
Axillary LN Dissection
Radiation to Chest Wall
and Regional LN
Adjuvant Endocrine Rx (HR+)
+/or Trastuzumab (HER2+)
Nakhlis 2016
Overall survival
86%
51%
Time to tumor recurrence
79%
33%
Retrospective Studies of Preoperative
Chemotherapy for IBC
No.
IBC
Chemotherapy RR Median
Survival
Italy 68 CAF or CEF / CMF pCR: 3% 4 yr.
U Penn 52 CMF +/- CAF pCR: 12% NR
France 120 FEC-HD pCR: 15% 5 yr.
British Columbia 308 CT v intensive CT (+ T) pCR:
28% v 33%
3.2 yr.
MD Anderson 240 FAC v FAC + T pCR:
10% v 25%
3.4 v 4.3 yr
Primary chemotherapy backbone = anthracycline and taxane
Dose-Dense versus Conventional Preoperative
Chemotherapy (AGO-1) – Overall ≠ IBC
• 668 patients with locally advanced breast cancer
• Overall group benefitted from intensive
chemotherapy:
• Improved pCR – 18% vs 10%
• Improved time to disease recurrence
• Improved overall survival
Untch M JCO 2009; 27:2938
• 100 IBC
• No difference with intensity of chemotherapy:
• No difference in pCR – 12% vs 10%
• No difference in time to disease recurrence
• No difference in overall survival
≠
pCR Rates in SWOG 0012: Standard AC versus
“Continuous” AC
Georgiana K. Ellis et al. JCO 2011;29:1014-1021
• 356 Overall vs 111 IBC (31%)
• Overall: no difference in outcome
• Higher pCR in IBC with continuous dosing of chemotherapy – 27% vs 13%
Finding Therapeutic Targets in IBC
•HER-2
•Angiogenesis
•JAK2-STAT3
Finding Therapeutic Targets in IBC
•Targeting HER-2
•Angiogenesis
•JAK2-STAT3
NOAH – IBC Experience
64% v 24%
74% v 44%
5-YR EFS
5-YR OS
Doxorubicin
60mg/m2 →
Paclitaxel
150mg/m2 q21d x 3
Paclitaxel
175mg/m2 q21d x 4
CMF x 3
Subset Analysis
• 61 / 228 pts with IBC,
HER2+
• pCR = 48 % with
trastuzumab
•13% without trastuzumab
Gianni L. Lancet Oncol 2014 15:640
Anti-HER2 Therapy
Trypheana (13/225
= 6% IBC)
FEC+HP x 3 →T+HP x 3
(N=73)
FEC x 3 → T+HP x 3
(N=75)
TCH+P x 6
(N=77)
IBC 5(7%) 4(5%) 4(5%)
tpCR 41(56%) 41(55%) 48(64%)
NeoSphere
(29/417 = 7% IBC)
T+D (N=107) T+D+P (N=107) T+P (N=107) P+D (N=96)
IBC* 7 (7%) 10 (9%) 7 (7%) 5 (5%)
tpCR (all) 23 (22%) 42 (40%) 12 (11%) 17 (18%)
5y –DFS 81% 84% 80% 75%
Gianni Lancet Oncol 2012;13:25-32; Schneeweiss Ann Oncol 2013;2278-84; Gianni Lancet Oncol 2016; Gianni Lancet Oncol 2012;
Boussen, JCO 2010; Untch Lancet Onc 2012.
Investigating lapatinib Regimen Number enrolled pCR
MDACC Lapatinib +
paclitaxel
32 3/17 (18%)
GeparQuinto EC→D
(L v H)
82/620 =13% IBC 23% v 30% (p=0.04)
Odds ratio IBC = 0.72 (NS)
Run In Phase – Day 1 week 1 (breast biopsy #1)
Pertuzumab IV 840 mg loading dose Trastuzumab IV 4 mg/kg loading
dose
Treatment Phase – Day 8 week 2 (breast biopsy #2)
Trastuzumab IV 2mg/kg weekly and paclitaxel 80 mg/m2 IV weekly x 16 weeks.
Day 21 week 4
Continue trastuzumab and paclitaxel as above and begin pertuzumab 420 mg IV
every 21 days for 5 doses
Modified radical mastectomy
(assess residual disease)
Post-operative Treatment:
Doxorubicin 60 mg/m2 IV and cyclophosphamide 600 mg/m2 IV every 3 weeks x 4 cycles*
Followed by trastuzumab 6 mg/kg and pertuzumab 420 mg every 21 days x 8 months**
(loading dose given first after AC completed)
Radiation Therapy
Endocrine therapy if HR+
*Optional
**Metastatic disease (nodal disease only):
continue on pertuzumab + trastuzumab
until disease progression
Primary Objective: pCR
• Accept benefit if > 8/ 27
pts have pCR
NCI-2013-01110, NCT0179619712-497; Genentech, IBC Network - sponsor
Hypothesis:
Can we limit the amount
of chemotherapy and
maximize the HER2-
directed therapy in the
treatment of HER2+ IBC ?
Finding Therapeutic Targets in IBC
•Targeting HER-2
•Angiogenesis
•JAK2-STAT3
Angiogenesis and Lymphangiogenesis in IBC
• IBC makes its own blood supply and
lymphatic supply throughout the
breast
• Increased expression of
angiogenesis related genes
• Increased expression of
lymphangiogenesis related genes
• Is this “encircling
lymphovasculogenesis” or
lymphovascular invasion ?
Colpaert CG, Br J Ca 2003;88:718; Van der Auwera Clin Can Res 2005;11:7637
Angiogenesis in IBC: Is it a Useful Target ?
Addition of Anti-angiogenic Agents to Pre-operative Chemotherapy
Treatment Number Stage pCR Median
DFS (III)
Correlatives
SU5416, doxorubicin 17 III or IV 0 32 mo DCE/MRI –
(Kep) – 58%
(p=0.033)
Bevacizumab,
docetaxel,
doxorubicin
21 (1 LABC) III or IV 1 (5%) 25.3 mo DCE-MRI –
(Ktrans) – 34%
(p=.003)
BEVERLY-1 (FEC(B) x
4 → D(B) x 4)
100 III 19 (19%) 53 mo CTC not
associated with
pCR
BEVERLY-2 (FEC(B) x
4 → D(B+H) x 4)
52 III 33 (64%) NA CTC not
associated with
pCR
Overmoyer CCR 2007; Wedam JCO 2006; Bertucci 2016; Pierga 2012
Eribulin and Normalization of Vasculature
Region of Interest (ROI) Ktrans (1/min/1000)
Pre-Eribulin Post-Eribulin (d 8)
#1 ROI 78.1 115.2
#2 ROI 47.5 71.4
• Eribulin effects on mice:
• Improves blood flow to inside of tumor
• Increased overall tumor blood flow
• Changes in expression of genes for blood
vessel formation and cancer survival
• In IBC – investigate eribulin’s effect on tumor
blood flow
• Also investigate expression on genes for
blood vessel formation and cancer survival
2
1
Agoulnik Vasc Cell 2014.; Funahashi Cancer Sci 2014; Yoshida Br J Cancer 2014.; Dezso PLoS One 2014.; Overmoyer SABCS 2016.
2
1
Pre-treatment breast biopsy #1
Eribulin x 1 (cycle 1 day 1)
Breast biopsy #2: 1 wk after eribulin
(cycle 1 day 8)
Eribulin q 3 wks x 3 cycles
dd AC q 2 wks x 4 cycles
Mastectomy (harvest residual tumor)
Radiation therapy + endocrine therapy
Imaging subset study
Pre-treatment
breast DCE-MRI
1 wk after eribulin
(c1,d8) breast DCE-
MRI
Eribulin
1.4mg/m2 IV
d1,d8 q21d x 4
cycles
Doxorubicin 60
mg/m2 +
cyclophosphamide
600 mg/m2 IV q2w x
4 cycles
Overview
• Primary Objective: pCR rate
• Two-stage design:
• Reject if pCR is < 15%
• Accept if pCR > 30%
• > 2/16 pCR – go forward
• Accept benefit if > 5/ 25 pts
have pCR
NCI-2016-00329, NCT0262397215-292; Eisai-sponsor
Finding Therapeutic Targets in IBC
•Targeting HER-2
•Angiogenesis
•JAK2-STAT3
Slides curtesy of Kornelia Polyak MD, PhD
N=64
(50 +)
Ruxolitinib x 7
days
(N=32)
Ruxolitinib x 7d +
Paclitaxel x 1 wk
(N=32)
Paclitaxel x 12
weeks (N=16)
Ruxolitinib +
Paclitaxel x 12
weeks (N=16)
Ruxolitinib +
Paclitaxel x 11
weeks (N=32)
dd doxorubicin/cyclophosphamide x
4 cycles (N=64)
Modified radical mastectomy
Radiation therapy
Pre-treatment biopsy #1
Post-run-in biopsy #2
Primary:
Pharmacodynamic
Secondary:
Clinical
TBCRC 039 - SCHEME
Sponsored by Incyte, and
Inflammatory Breast Cancer Research Foundation
Primary Systemic Therapy for IBC:
Beginning the Journey
• IBC is inoperable at the time of diagnosis, therefore initial therapy with
“systemic treatment” is indicated.
• IBC is relatively chemo-resistant, therefore identifying therapeutic targets is
critical.
• We must focus our efforts on designing clinical trials specifically for IBC
• Inclusion of IBC patients into LABC trials will dilute the interpretation of
outcome
• Incorporate translational components
• Identify biologic markers that confirm the diagnosis, not just rely on “clinical
features” that are not consistent.

More Related Content

What's hot

Management of carcinoma breast2013
Management of carcinoma breast2013Management of carcinoma breast2013
Management of carcinoma breast2013
Sumer Yadav
 
Treatment of breast cancer by Dr.Syed Alam Zeb
Treatment of breast cancer by Dr.Syed Alam ZebTreatment of breast cancer by Dr.Syed Alam Zeb
Treatment of breast cancer by Dr.Syed Alam Zeb
Syed Alam Zeb
 
BCT - AIIMS Experience
BCT - AIIMS ExperienceBCT - AIIMS Experience
BCT - AIIMS Experience
guest8887a7
 

What's hot (20)

Surgery for Inflammatory Breast Cancer: How and Why
Surgery for Inflammatory Breast Cancer: How and WhySurgery for Inflammatory Breast Cancer: How and Why
Surgery for Inflammatory Breast Cancer: How and Why
 
DCIS Breast Cancer
DCIS Breast CancerDCIS Breast Cancer
DCIS Breast Cancer
 
Locally advanced ca breast LABC
Locally advanced ca breast LABCLocally advanced ca breast LABC
Locally advanced ca breast LABC
 
Early Stage Breast Cancer and Radiation Therapy
Early Stage Breast Cancer and Radiation TherapyEarly Stage Breast Cancer and Radiation Therapy
Early Stage Breast Cancer and Radiation Therapy
 
Locally advanced breast cancer management
Locally advanced breast cancer managementLocally advanced breast cancer management
Locally advanced breast cancer management
 
Locally advanced breast cancer
Locally advanced breast cancerLocally advanced breast cancer
Locally advanced breast cancer
 
Management of breast cancer
Management of breast cancerManagement of breast cancer
Management of breast cancer
 
Management of carcinoma breast2013
Management of carcinoma breast2013Management of carcinoma breast2013
Management of carcinoma breast2013
 
Treatment of breast cancer by Dr.Syed Alam Zeb
Treatment of breast cancer by Dr.Syed Alam ZebTreatment of breast cancer by Dr.Syed Alam Zeb
Treatment of breast cancer by Dr.Syed Alam Zeb
 
LANDMARK TRIALS IN BREAST CANCER
LANDMARK TRIALS IN BREAST CANCERLANDMARK TRIALS IN BREAST CANCER
LANDMARK TRIALS IN BREAST CANCER
 
Dr arun Triple Negative Breast cancer Presentation
Dr arun Triple Negative Breast cancer PresentationDr arun Triple Negative Breast cancer Presentation
Dr arun Triple Negative Breast cancer Presentation
 
Hyperthermic intraperitoneal chemotherapy
Hyperthermic intraperitoneal chemotherapyHyperthermic intraperitoneal chemotherapy
Hyperthermic intraperitoneal chemotherapy
 
BCT - AIIMS Experience
BCT - AIIMS ExperienceBCT - AIIMS Experience
BCT - AIIMS Experience
 
Management of Early Breast Cancer (by Dr. Akhil Kapoor)
Management of Early Breast Cancer (by Dr. Akhil Kapoor)Management of Early Breast Cancer (by Dr. Akhil Kapoor)
Management of Early Breast Cancer (by Dr. Akhil Kapoor)
 
Hyperthermic Intraperitoneal Chemotherapy for Peritoneal Surface Malignancies
Hyperthermic Intraperitoneal Chemotherapy for Peritoneal Surface MalignanciesHyperthermic Intraperitoneal Chemotherapy for Peritoneal Surface Malignancies
Hyperthermic Intraperitoneal Chemotherapy for Peritoneal Surface Malignancies
 
EARLY BREAST CANCER Sohini
EARLY BREAST CANCER SohiniEARLY BREAST CANCER Sohini
EARLY BREAST CANCER Sohini
 
Trials in esophageal cancer.pptx
Trials in esophageal cancer.pptxTrials in esophageal cancer.pptx
Trials in esophageal cancer.pptx
 
Ca vagina & vulva
Ca vagina & vulva Ca vagina & vulva
Ca vagina & vulva
 
Peritoneal Carcinomatosis : Dr Amit Dangi
Peritoneal Carcinomatosis :  Dr Amit DangiPeritoneal Carcinomatosis :  Dr Amit Dangi
Peritoneal Carcinomatosis : Dr Amit Dangi
 
Strategies for Managing Recurrent Ovarian Cancer
Strategies for Managing Recurrent Ovarian CancerStrategies for Managing Recurrent Ovarian Cancer
Strategies for Managing Recurrent Ovarian Cancer
 

Similar to Primary Systemic Therapy for Inflammatory Breast Cancer

Noa Efrat Ben Baruch : Neo-adjuvant treatment in breast cancer
Noa Efrat Ben Baruch : Neo-adjuvant treatment in breast cancerNoa Efrat Ben Baruch : Neo-adjuvant treatment in breast cancer
Noa Efrat Ben Baruch : Neo-adjuvant treatment in breast cancer
breastcancerupdatecongress
 
BALKAN MCO 2011 - A. Eniu - How to optimize systemic therapy in LABC
BALKAN MCO 2011 - A. Eniu - How to optimize systemic therapy in LABC BALKAN MCO 2011 - A. Eniu - How to optimize systemic therapy in LABC
BALKAN MCO 2011 - A. Eniu - How to optimize systemic therapy in LABC
European School of Oncology
 
Post mastectomy Radiotherapy with trails
Post mastectomy Radiotherapy with trailsPost mastectomy Radiotherapy with trails
Post mastectomy Radiotherapy with trails
Anban Bala
 
NSCLC housestaff
NSCLC housestaffNSCLC housestaff
NSCLC housestaff
derosaMSKCC
 
Product Visual Guide
Product Visual GuideProduct Visual Guide
Product Visual Guide
Manas Tandon
 

Similar to Primary Systemic Therapy for Inflammatory Breast Cancer (20)

esmo breast chemotherapy curigliano 02.05.2022.pptx
esmo breast chemotherapy curigliano 02.05.2022.pptxesmo breast chemotherapy curigliano 02.05.2022.pptx
esmo breast chemotherapy curigliano 02.05.2022.pptx
 
Noa Efrat Ben Baruch : Neo-adjuvant treatment in breast cancer
Noa Efrat Ben Baruch : Neo-adjuvant treatment in breast cancerNoa Efrat Ben Baruch : Neo-adjuvant treatment in breast cancer
Noa Efrat Ben Baruch : Neo-adjuvant treatment in breast cancer
 
Cervical cancer
Cervical cancerCervical cancer
Cervical cancer
 
How I treat Relapsed Ca Ovary
How I treat Relapsed Ca OvaryHow I treat Relapsed Ca Ovary
How I treat Relapsed Ca Ovary
 
Ovarian Cancer 101
Ovarian Cancer 101Ovarian Cancer 101
Ovarian Cancer 101
 
CCO_Head_and_Neck_Cancer_Clinical_Impact_ExpressPts.pptx
CCO_Head_and_Neck_Cancer_Clinical_Impact_ExpressPts.pptxCCO_Head_and_Neck_Cancer_Clinical_Impact_ExpressPts.pptx
CCO_Head_and_Neck_Cancer_Clinical_Impact_ExpressPts.pptx
 
Colorectal Cancer Research & Treatment News - recap from the May 2014 ASCO co...
Colorectal Cancer Research & Treatment News - recap from the May 2014 ASCO co...Colorectal Cancer Research & Treatment News - recap from the May 2014 ASCO co...
Colorectal Cancer Research & Treatment News - recap from the May 2014 ASCO co...
 
Report Back from San Antonio Breast Cancer Symposium (SABCS 2022)
Report Back from San Antonio Breast Cancer Symposium (SABCS 2022)Report Back from San Antonio Breast Cancer Symposium (SABCS 2022)
Report Back from San Antonio Breast Cancer Symposium (SABCS 2022)
 
BALKAN MCO 2011 - A. Eniu - How to optimize systemic therapy in LABC
BALKAN MCO 2011 - A. Eniu - How to optimize systemic therapy in LABC BALKAN MCO 2011 - A. Eniu - How to optimize systemic therapy in LABC
BALKAN MCO 2011 - A. Eniu - How to optimize systemic therapy in LABC
 
Jean Yves Pierga ASCO 2015
Jean Yves Pierga ASCO 2015Jean Yves Pierga ASCO 2015
Jean Yves Pierga ASCO 2015
 
Research Update on MBC
Research Update on MBCResearch Update on MBC
Research Update on MBC
 
Post mastectomy Radiotherapy with trails
Post mastectomy Radiotherapy with trailsPost mastectomy Radiotherapy with trails
Post mastectomy Radiotherapy with trails
 
NSCLC housestaff
NSCLC housestaffNSCLC housestaff
NSCLC housestaff
 
Managment of Cervical Cancer
Managment of Cervical CancerManagment of Cervical Cancer
Managment of Cervical Cancer
 
Gi Cancer Symposium 2012 Report Presentation
Gi Cancer Symposium 2012 Report PresentationGi Cancer Symposium 2012 Report Presentation
Gi Cancer Symposium 2012 Report Presentation
 
Product Visual Guide
Product Visual GuideProduct Visual Guide
Product Visual Guide
 
Triple Negative Breast Cancer
Triple Negative Breast CancerTriple Negative Breast Cancer
Triple Negative Breast Cancer
 
Hipec for metastatic colorectal cancers
Hipec for metastatic colorectal cancersHipec for metastatic colorectal cancers
Hipec for metastatic colorectal cancers
 
Rectal cancer debate: Chemoradiation
Rectal cancer debate: ChemoradiationRectal cancer debate: Chemoradiation
Rectal cancer debate: Chemoradiation
 
CORALLEEN phase 2 trial: Neoadjuvant Ribociclib plus Letrozole in Early Stage...
CORALLEEN phase 2 trial: Neoadjuvant Ribociclib plus Letrozole in Early Stage...CORALLEEN phase 2 trial: Neoadjuvant Ribociclib plus Letrozole in Early Stage...
CORALLEEN phase 2 trial: Neoadjuvant Ribociclib plus Letrozole in Early Stage...
 

More from Dana-Farber Cancer Institute

More from Dana-Farber Cancer Institute (20)

Exercise Tips for Cancer Patients
Exercise Tips for Cancer Patients Exercise Tips for Cancer Patients
Exercise Tips for Cancer Patients
 
Personal Finance Tips for Young Adults with Cancer
Personal Finance Tips for Young Adults with Cancer Personal Finance Tips for Young Adults with Cancer
Personal Finance Tips for Young Adults with Cancer
 
5 Things to Know About Glioblastomas
5 Things to Know About Glioblastomas5 Things to Know About Glioblastomas
5 Things to Know About Glioblastomas
 
How are Adult and Childhood Leukemia Alike and Different?
How are Adult and Childhood Leukemia Alike and Different?How are Adult and Childhood Leukemia Alike and Different?
How are Adult and Childhood Leukemia Alike and Different?
 
Research in the Program for Young Women with Breast Cancer: Past, Present and...
Research in the Program for Young Women with Breast Cancer: Past, Present and...Research in the Program for Young Women with Breast Cancer: Past, Present and...
Research in the Program for Young Women with Breast Cancer: Past, Present and...
 
Clinical Trials for Metastatic HER2-positive Breast Cancer
Clinical Trials for Metastatic HER2-positive Breast CancerClinical Trials for Metastatic HER2-positive Breast Cancer
Clinical Trials for Metastatic HER2-positive Breast Cancer
 
Clinical Trials for Metastatic Triple-Negative Breast Cancer
Clinical Trials for Metastatic Triple-Negative Breast CancerClinical Trials for Metastatic Triple-Negative Breast Cancer
Clinical Trials for Metastatic Triple-Negative Breast Cancer
 
Healthy Living After A Breast Cancer Diagnosis
Healthy Living After A Breast Cancer DiagnosisHealthy Living After A Breast Cancer Diagnosis
Healthy Living After A Breast Cancer Diagnosis
 
Signs and Symptoms of Prostate Cancer
Signs and Symptoms of Prostate CancerSigns and Symptoms of Prostate Cancer
Signs and Symptoms of Prostate Cancer
 
6 Common Types of Pediatric Brain Tumors
6 Common Types of Pediatric Brain Tumors6 Common Types of Pediatric Brain Tumors
6 Common Types of Pediatric Brain Tumors
 
Soft Tissue Sarcomas: Symptoms and Risk Factors
Soft Tissue Sarcomas: Symptoms and Risk FactorsSoft Tissue Sarcomas: Symptoms and Risk Factors
Soft Tissue Sarcomas: Symptoms and Risk Factors
 
10 Tips for Easing Chemo-Related Fatigue
10 Tips for Easing Chemo-Related Fatigue10 Tips for Easing Chemo-Related Fatigue
10 Tips for Easing Chemo-Related Fatigue
 
Radiation Therapy for Inflammatory Breast Cancer
Radiation Therapy for Inflammatory Breast CancerRadiation Therapy for Inflammatory Breast Cancer
Radiation Therapy for Inflammatory Breast Cancer
 
What Cancers Should Men Be Screened For?
What Cancers Should Men Be Screened For?What Cancers Should Men Be Screened For?
What Cancers Should Men Be Screened For?
 
Five Common Types of Brain Tumors
Five Common Types of Brain TumorsFive Common Types of Brain Tumors
Five Common Types of Brain Tumors
 
Signs and Symptoms of Multiple Myeloma
Signs and Symptoms of Multiple MyelomaSigns and Symptoms of Multiple Myeloma
Signs and Symptoms of Multiple Myeloma
 
7 Ways Integrative Therapies Can Help Cancer Patients
7 Ways Integrative Therapies Can Help Cancer Patients7 Ways Integrative Therapies Can Help Cancer Patients
7 Ways Integrative Therapies Can Help Cancer Patients
 
Five Things You Need to Know About Colon Cancer
Five Things You Need to Know About Colon CancerFive Things You Need to Know About Colon Cancer
Five Things You Need to Know About Colon Cancer
 
What You Should Know About Cervical Cancer
What You Should Know About Cervical CancerWhat You Should Know About Cervical Cancer
What You Should Know About Cervical Cancer
 
Making A New Treatment Decision
Making A New Treatment DecisionMaking A New Treatment Decision
Making A New Treatment Decision
 

Recently uploaded

Healthcare Market Overview, May 2024: Funding, Financing and M&A, from Oppenh...
Healthcare Market Overview, May 2024: Funding, Financing and M&A, from Oppenh...Healthcare Market Overview, May 2024: Funding, Financing and M&A, from Oppenh...
Healthcare Market Overview, May 2024: Funding, Financing and M&A, from Oppenh...
Levi Shapiro
 
Jual obat aborsi Salatiga Wa 081225888346 obat aborsi Cytotec asli Di Salatiga
Jual obat aborsi Salatiga Wa 081225888346 obat aborsi Cytotec asli Di SalatigaJual obat aborsi Salatiga Wa 081225888346 obat aborsi Cytotec asli Di Salatiga
Jual obat aborsi Salatiga Wa 081225888346 obat aborsi Cytotec asli Di Salatiga
aureliamarcelin589
 
Abortion pills in Abu Dhabi ௵+918133066128௹Un_wandted Pregnancy Kit in Dubai UAE
Abortion pills in Abu Dhabi ௵+918133066128௹Un_wandted Pregnancy Kit in Dubai UAEAbortion pills in Abu Dhabi ௵+918133066128௹Un_wandted Pregnancy Kit in Dubai UAE
Abortion pills in Abu Dhabi ௵+918133066128௹Un_wandted Pregnancy Kit in Dubai UAE
Abortion pills in Kuwait Cytotec pills in Kuwait
 
Cara menggugurkan kandungan paling ampuh 08561234742
Cara menggugurkan kandungan paling ampuh 08561234742Cara menggugurkan kandungan paling ampuh 08561234742
Cara menggugurkan kandungan paling ampuh 08561234742
Jual obat penggugur 08561234742 Cara menggugurkan kandungan 08561234742
 
ITM HOSPITAL The hospital has also been recognised as the best emerging hosp...
ITM  HOSPITAL The hospital has also been recognised as the best emerging hosp...ITM  HOSPITAL The hospital has also been recognised as the best emerging hosp...
ITM HOSPITAL The hospital has also been recognised as the best emerging hosp...
jvomprakash
 
Catheterization Procedure by Anushri Srivastav.pptx
Catheterization Procedure by Anushri Srivastav.pptxCatheterization Procedure by Anushri Srivastav.pptx
Catheterization Procedure by Anushri Srivastav.pptx
AnushriSrivastav
 
INTERNATIONAL HEALTH AGENCIES BY ANUSHRI SRIVASTAV.pptx
INTERNATIONAL HEALTH AGENCIES BY ANUSHRI SRIVASTAV.pptxINTERNATIONAL HEALTH AGENCIES BY ANUSHRI SRIVASTAV.pptx
INTERNATIONAL HEALTH AGENCIES BY ANUSHRI SRIVASTAV.pptx
AnushriSrivastav
 

Recently uploaded (20)

Healthcare Market Overview, May 2024: Funding, Financing and M&A, from Oppenh...
Healthcare Market Overview, May 2024: Funding, Financing and M&A, from Oppenh...Healthcare Market Overview, May 2024: Funding, Financing and M&A, from Oppenh...
Healthcare Market Overview, May 2024: Funding, Financing and M&A, from Oppenh...
 
Jual obat aborsi Salatiga Wa 081225888346 obat aborsi Cytotec asli Di Salatiga
Jual obat aborsi Salatiga Wa 081225888346 obat aborsi Cytotec asli Di SalatigaJual obat aborsi Salatiga Wa 081225888346 obat aborsi Cytotec asli Di Salatiga
Jual obat aborsi Salatiga Wa 081225888346 obat aborsi Cytotec asli Di Salatiga
 
Australia,USA,UK #Online psychic ,"£ +27834335081 Canada Lost Love Spell Cast...
Australia,USA,UK #Online psychic ,"£ +27834335081 Canada Lost Love Spell Cast...Australia,USA,UK #Online psychic ,"£ +27834335081 Canada Lost Love Spell Cast...
Australia,USA,UK #Online psychic ,"£ +27834335081 Canada Lost Love Spell Cast...
 
Abortion pills in Abu Dhabi ௵+918133066128௹Un_wandted Pregnancy Kit in Dubai UAE
Abortion pills in Abu Dhabi ௵+918133066128௹Un_wandted Pregnancy Kit in Dubai UAEAbortion pills in Abu Dhabi ௵+918133066128௹Un_wandted Pregnancy Kit in Dubai UAE
Abortion pills in Abu Dhabi ௵+918133066128௹Un_wandted Pregnancy Kit in Dubai UAE
 
Cara menggugurkan kandungan paling ampuh 08561234742
Cara menggugurkan kandungan paling ampuh 08561234742Cara menggugurkan kandungan paling ampuh 08561234742
Cara menggugurkan kandungan paling ampuh 08561234742
 
VIP ℂall Girls Sushant Lok 9873777170 WhatsApp: Me All Time Serviℂe Available
VIP ℂall Girls Sushant Lok 9873777170 WhatsApp: Me All Time Serviℂe AvailableVIP ℂall Girls Sushant Lok 9873777170 WhatsApp: Me All Time Serviℂe Available
VIP ℂall Girls Sushant Lok 9873777170 WhatsApp: Me All Time Serviℂe Available
 
ITM HOSPITAL The hospital has also been recognised as the best emerging hosp...
ITM  HOSPITAL The hospital has also been recognised as the best emerging hosp...ITM  HOSPITAL The hospital has also been recognised as the best emerging hosp...
ITM HOSPITAL The hospital has also been recognised as the best emerging hosp...
 
mHealth Israel_Healthcare Finance and M&A- What Comes Next
mHealth Israel_Healthcare Finance and M&A- What Comes NextmHealth Israel_Healthcare Finance and M&A- What Comes Next
mHealth Israel_Healthcare Finance and M&A- What Comes Next
 
End of Response issues - Code and Rapid Response Workshop
End of Response issues - Code and Rapid Response WorkshopEnd of Response issues - Code and Rapid Response Workshop
End of Response issues - Code and Rapid Response Workshop
 
Catheterization Procedure by Anushri Srivastav.pptx
Catheterization Procedure by Anushri Srivastav.pptxCatheterization Procedure by Anushri Srivastav.pptx
Catheterization Procedure by Anushri Srivastav.pptx
 
Adrenal Function Tests-3.pptxwhfbdqbfwwfjgwngnegenhndngssfb
Adrenal Function Tests-3.pptxwhfbdqbfwwfjgwngnegenhndngssfbAdrenal Function Tests-3.pptxwhfbdqbfwwfjgwngnegenhndngssfb
Adrenal Function Tests-3.pptxwhfbdqbfwwfjgwngnegenhndngssfb
 
Indore 💋 ℂall Girl 9713632684 ℂall Girls in Indore Esℂort serviℂe book now
Indore 💋 ℂall Girl 9713632684 ℂall Girls in Indore Esℂort serviℂe book nowIndore 💋 ℂall Girl 9713632684 ℂall Girls in Indore Esℂort serviℂe book now
Indore 💋 ℂall Girl 9713632684 ℂall Girls in Indore Esℂort serviℂe book now
 
Abortion pills in Kuwait (+918133066128) Abortion clinic pills in Kuwait
Abortion pills in Kuwait (+918133066128) Abortion clinic pills in KuwaitAbortion pills in Kuwait (+918133066128) Abortion clinic pills in Kuwait
Abortion pills in Kuwait (+918133066128) Abortion clinic pills in Kuwait
 
An overview of Muir Wood Adolescent and Family Services teen treatment progra...
An overview of Muir Wood Adolescent and Family Services teen treatment progra...An overview of Muir Wood Adolescent and Family Services teen treatment progra...
An overview of Muir Wood Adolescent and Family Services teen treatment progra...
 
INTERNATIONAL HEALTH AGENCIES BY ANUSHRI SRIVASTAV.pptx
INTERNATIONAL HEALTH AGENCIES BY ANUSHRI SRIVASTAV.pptxINTERNATIONAL HEALTH AGENCIES BY ANUSHRI SRIVASTAV.pptx
INTERNATIONAL HEALTH AGENCIES BY ANUSHRI SRIVASTAV.pptx
 
Session-5-Birthing-Practices-Breastfeeding (1).ppt
Session-5-Birthing-Practices-Breastfeeding (1).pptSession-5-Birthing-Practices-Breastfeeding (1).ppt
Session-5-Birthing-Practices-Breastfeeding (1).ppt
 
Session-3-Promoting-Breastfeeding-During-Pregnancy.ppt
Session-3-Promoting-Breastfeeding-During-Pregnancy.pptSession-3-Promoting-Breastfeeding-During-Pregnancy.ppt
Session-3-Promoting-Breastfeeding-During-Pregnancy.ppt
 
Antiepileptic-Drugs-and-Congenital-Anomalies copy.pptx
Antiepileptic-Drugs-and-Congenital-Anomalies copy.pptxAntiepileptic-Drugs-and-Congenital-Anomalies copy.pptx
Antiepileptic-Drugs-and-Congenital-Anomalies copy.pptx
 
Personnel and Equipment - Code and Rapid Response Workshop
Personnel and Equipment - Code and Rapid Response WorkshopPersonnel and Equipment - Code and Rapid Response Workshop
Personnel and Equipment - Code and Rapid Response Workshop
 
Unlock the Secrets to Optimizing Ambulatory Operations Efficiency and Change ...
Unlock the Secrets to Optimizing Ambulatory Operations Efficiency and Change ...Unlock the Secrets to Optimizing Ambulatory Operations Efficiency and Change ...
Unlock the Secrets to Optimizing Ambulatory Operations Efficiency and Change ...
 

Primary Systemic Therapy for Inflammatory Breast Cancer

  • 1. Primary Systemic Therapy: Beginning the Journey Beth Overmoyer MD, FACP Director, Inflammatory Breast Cancer Program 1st Annual IBC Patient Forum Dana Farber Cancer Institute May 13, 2017
  • 2. Historical Perspective of IBC • The historical identification of IBC is important as a reminder of the acceptance of classic clinical criteria that differentiates the disease from other forms of locally advanced breast cancer • 1814 – Sir Charles Bell described a grave prognosis associated with breast cancer when the following characteristics are present: • “when a purple color is on the skin over the tumor accompanied by shooting pains it is a very unpropitious beginning” • Lee and Tannenbaum (1924) – “inflammatory breast cancer”
  • 3. IBC – A Distinct Subtype of Breast Cancer Distinct subtype of breast cancer • Definitive or pathologic diagnostic criteria do not exist • “Clinical diagnosis” fraught with potential problems, both underestimating and overestimating the diagnosis • Seer 2004-7: 2-yr BCS • IBC = 84% • LABC = 91% • 43% higher risk of breast cancer death in IBC vs. LABC • German study: 4.5x greater risk of dying within 5 years Diessner Arch Gyn Obs 2015;292:655; Anderson WF, JCO 21:2254, 2003 IBC LABC
  • 4. • 1-5% incidence in US • Difficulty in tracking the disease due to variation in diagnostic criteria over time • Underestimate incidence Clinical definition with confirmed breast cancer: Rapid onset – 3 – 6 mo • Erythema > 1/3 breast • Edema (peau d’orange) • Often warm breast, pain • Breast enlargement – often without a mass • Highly metastatic: 35% metastasis at presentation Clinical Presentation - IBC
  • 5. Clinical Diagnosis of IBC • Tumor emboli in dermal lymphatics without classical signs is not considered IBC • The presence of dermal lymphatic invasion is not necessary for the diagnosis of IBC
  • 6. “Trimodality” Therapy: Importance of pCR Primary Systemic Therapy Mastectomy + Axillary LN Dissection Radiation to Chest Wall and Regional LN Adjuvant Endocrine Rx (HR+) +/or Trastuzumab (HER2+) Nakhlis 2016 Overall survival 86% 51% Time to tumor recurrence 79% 33%
  • 7. Retrospective Studies of Preoperative Chemotherapy for IBC No. IBC Chemotherapy RR Median Survival Italy 68 CAF or CEF / CMF pCR: 3% 4 yr. U Penn 52 CMF +/- CAF pCR: 12% NR France 120 FEC-HD pCR: 15% 5 yr. British Columbia 308 CT v intensive CT (+ T) pCR: 28% v 33% 3.2 yr. MD Anderson 240 FAC v FAC + T pCR: 10% v 25% 3.4 v 4.3 yr Primary chemotherapy backbone = anthracycline and taxane
  • 8. Dose-Dense versus Conventional Preoperative Chemotherapy (AGO-1) – Overall ≠ IBC • 668 patients with locally advanced breast cancer • Overall group benefitted from intensive chemotherapy: • Improved pCR – 18% vs 10% • Improved time to disease recurrence • Improved overall survival Untch M JCO 2009; 27:2938 • 100 IBC • No difference with intensity of chemotherapy: • No difference in pCR – 12% vs 10% • No difference in time to disease recurrence • No difference in overall survival ≠
  • 9. pCR Rates in SWOG 0012: Standard AC versus “Continuous” AC Georgiana K. Ellis et al. JCO 2011;29:1014-1021 • 356 Overall vs 111 IBC (31%) • Overall: no difference in outcome • Higher pCR in IBC with continuous dosing of chemotherapy – 27% vs 13%
  • 10. Finding Therapeutic Targets in IBC •HER-2 •Angiogenesis •JAK2-STAT3
  • 11. Finding Therapeutic Targets in IBC •Targeting HER-2 •Angiogenesis •JAK2-STAT3
  • 12. NOAH – IBC Experience 64% v 24% 74% v 44% 5-YR EFS 5-YR OS Doxorubicin 60mg/m2 → Paclitaxel 150mg/m2 q21d x 3 Paclitaxel 175mg/m2 q21d x 4 CMF x 3 Subset Analysis • 61 / 228 pts with IBC, HER2+ • pCR = 48 % with trastuzumab •13% without trastuzumab Gianni L. Lancet Oncol 2014 15:640
  • 13. Anti-HER2 Therapy Trypheana (13/225 = 6% IBC) FEC+HP x 3 →T+HP x 3 (N=73) FEC x 3 → T+HP x 3 (N=75) TCH+P x 6 (N=77) IBC 5(7%) 4(5%) 4(5%) tpCR 41(56%) 41(55%) 48(64%) NeoSphere (29/417 = 7% IBC) T+D (N=107) T+D+P (N=107) T+P (N=107) P+D (N=96) IBC* 7 (7%) 10 (9%) 7 (7%) 5 (5%) tpCR (all) 23 (22%) 42 (40%) 12 (11%) 17 (18%) 5y –DFS 81% 84% 80% 75% Gianni Lancet Oncol 2012;13:25-32; Schneeweiss Ann Oncol 2013;2278-84; Gianni Lancet Oncol 2016; Gianni Lancet Oncol 2012; Boussen, JCO 2010; Untch Lancet Onc 2012. Investigating lapatinib Regimen Number enrolled pCR MDACC Lapatinib + paclitaxel 32 3/17 (18%) GeparQuinto EC→D (L v H) 82/620 =13% IBC 23% v 30% (p=0.04) Odds ratio IBC = 0.72 (NS)
  • 14. Run In Phase – Day 1 week 1 (breast biopsy #1) Pertuzumab IV 840 mg loading dose Trastuzumab IV 4 mg/kg loading dose Treatment Phase – Day 8 week 2 (breast biopsy #2) Trastuzumab IV 2mg/kg weekly and paclitaxel 80 mg/m2 IV weekly x 16 weeks. Day 21 week 4 Continue trastuzumab and paclitaxel as above and begin pertuzumab 420 mg IV every 21 days for 5 doses Modified radical mastectomy (assess residual disease) Post-operative Treatment: Doxorubicin 60 mg/m2 IV and cyclophosphamide 600 mg/m2 IV every 3 weeks x 4 cycles* Followed by trastuzumab 6 mg/kg and pertuzumab 420 mg every 21 days x 8 months** (loading dose given first after AC completed) Radiation Therapy Endocrine therapy if HR+ *Optional **Metastatic disease (nodal disease only): continue on pertuzumab + trastuzumab until disease progression Primary Objective: pCR • Accept benefit if > 8/ 27 pts have pCR NCI-2013-01110, NCT0179619712-497; Genentech, IBC Network - sponsor Hypothesis: Can we limit the amount of chemotherapy and maximize the HER2- directed therapy in the treatment of HER2+ IBC ?
  • 15. Finding Therapeutic Targets in IBC •Targeting HER-2 •Angiogenesis •JAK2-STAT3
  • 16. Angiogenesis and Lymphangiogenesis in IBC • IBC makes its own blood supply and lymphatic supply throughout the breast • Increased expression of angiogenesis related genes • Increased expression of lymphangiogenesis related genes • Is this “encircling lymphovasculogenesis” or lymphovascular invasion ? Colpaert CG, Br J Ca 2003;88:718; Van der Auwera Clin Can Res 2005;11:7637
  • 17. Angiogenesis in IBC: Is it a Useful Target ? Addition of Anti-angiogenic Agents to Pre-operative Chemotherapy Treatment Number Stage pCR Median DFS (III) Correlatives SU5416, doxorubicin 17 III or IV 0 32 mo DCE/MRI – (Kep) – 58% (p=0.033) Bevacizumab, docetaxel, doxorubicin 21 (1 LABC) III or IV 1 (5%) 25.3 mo DCE-MRI – (Ktrans) – 34% (p=.003) BEVERLY-1 (FEC(B) x 4 → D(B) x 4) 100 III 19 (19%) 53 mo CTC not associated with pCR BEVERLY-2 (FEC(B) x 4 → D(B+H) x 4) 52 III 33 (64%) NA CTC not associated with pCR Overmoyer CCR 2007; Wedam JCO 2006; Bertucci 2016; Pierga 2012
  • 18. Eribulin and Normalization of Vasculature Region of Interest (ROI) Ktrans (1/min/1000) Pre-Eribulin Post-Eribulin (d 8) #1 ROI 78.1 115.2 #2 ROI 47.5 71.4 • Eribulin effects on mice: • Improves blood flow to inside of tumor • Increased overall tumor blood flow • Changes in expression of genes for blood vessel formation and cancer survival • In IBC – investigate eribulin’s effect on tumor blood flow • Also investigate expression on genes for blood vessel formation and cancer survival 2 1 Agoulnik Vasc Cell 2014.; Funahashi Cancer Sci 2014; Yoshida Br J Cancer 2014.; Dezso PLoS One 2014.; Overmoyer SABCS 2016. 2 1
  • 19. Pre-treatment breast biopsy #1 Eribulin x 1 (cycle 1 day 1) Breast biopsy #2: 1 wk after eribulin (cycle 1 day 8) Eribulin q 3 wks x 3 cycles dd AC q 2 wks x 4 cycles Mastectomy (harvest residual tumor) Radiation therapy + endocrine therapy Imaging subset study Pre-treatment breast DCE-MRI 1 wk after eribulin (c1,d8) breast DCE- MRI Eribulin 1.4mg/m2 IV d1,d8 q21d x 4 cycles Doxorubicin 60 mg/m2 + cyclophosphamide 600 mg/m2 IV q2w x 4 cycles Overview • Primary Objective: pCR rate • Two-stage design: • Reject if pCR is < 15% • Accept if pCR > 30% • > 2/16 pCR – go forward • Accept benefit if > 5/ 25 pts have pCR NCI-2016-00329, NCT0262397215-292; Eisai-sponsor
  • 20. Finding Therapeutic Targets in IBC •Targeting HER-2 •Angiogenesis •JAK2-STAT3
  • 21. Slides curtesy of Kornelia Polyak MD, PhD
  • 22. N=64 (50 +) Ruxolitinib x 7 days (N=32) Ruxolitinib x 7d + Paclitaxel x 1 wk (N=32) Paclitaxel x 12 weeks (N=16) Ruxolitinib + Paclitaxel x 12 weeks (N=16) Ruxolitinib + Paclitaxel x 11 weeks (N=32) dd doxorubicin/cyclophosphamide x 4 cycles (N=64) Modified radical mastectomy Radiation therapy Pre-treatment biopsy #1 Post-run-in biopsy #2 Primary: Pharmacodynamic Secondary: Clinical TBCRC 039 - SCHEME Sponsored by Incyte, and Inflammatory Breast Cancer Research Foundation
  • 23. Primary Systemic Therapy for IBC: Beginning the Journey • IBC is inoperable at the time of diagnosis, therefore initial therapy with “systemic treatment” is indicated. • IBC is relatively chemo-resistant, therefore identifying therapeutic targets is critical. • We must focus our efforts on designing clinical trials specifically for IBC • Inclusion of IBC patients into LABC trials will dilute the interpretation of outcome • Incorporate translational components • Identify biologic markers that confirm the diagnosis, not just rely on “clinical features” that are not consistent.