1.
Metastatic breast cancer
ASCO 2017-What’s new?
Anne Moore, MD and Linda Vahdat, MD
Weill Cornell Breast Center
SHARE Webinar
June 20, 2017

2.
Breast cancer in the US-2017
New esFmated data
• 3.5 million women are living with a history of
breast cancer
– EsFmate 35,000 men
• 155,000 women are living with a history of
metastaFc breast cancer
• 26,500 women are living 10 years or more with
metastaFc breast cancer
MarioPo, Cancer Epidemiol Biomarkers
Prev 2017;26:809

3.
Breast cancer in the US-2017
“With opFmal care, women with MBC can and
oYen do live for years with reasonable quality of
life, albeit undergoing constant treatment to
keep their disease under control.”
MarioPo, Cancer Epidemiol Biomarkers
Prev 2017;26:809

4.
What have we learned
in the past few years?

5.
Every breast cancer is different!
DC Koboldt et al. Nature 000, 1-10 (2012)
doi:10.1038/nature11412

6.
Although all individual breast cancers
are different, there are 4 groups
• Hormone receptor posiFve
– Luminal A
– Luminal B
• Hormone receptor negaFve
• Her 2 posiFve

7.
Every breast cancer is different and there are frequently
differences between the primary cancer and the metastasis
Biopsy of the metastasis is very important!
Amir E et al. JCO 2012;30:587-592

8.
Every breast cancer is different and there are frequently
differences between the primary cancer and the metastasis
Biopsy of the metastasis is very important!
Amir E et al. JCO 2012;30:587-592
37% of the Fme, the ER/
PR or HER 2 in the
metastasis is different
from the original primary
cancer

9.
Should all breast cancers, primary or metastaFc,
be tested for
“next generaFon sequencing”?
Precision Medicine analyses such as FoundaFon One
test for gene mutaFons in the cancer…
At present, this is not a rouFne analysis for breast
cancer. There was no new informaFon at ASCO that
leads me to think this should be done rouFnely.. But
keep asking!

10.
ASCO 2017
• Held in Chicago-almost 40,000 aPendees from
more than 150 countries.
• Papers with new findings about cancer were
submiPed and selected for presentaFon ---
almost 12,000 were published in the
Proceedings

11.
ASCO 2017-almost 12,000 abstracts

12.
ASCO 2017: Breast Cancer Highlights
Hormone receptor (ER and/or PR posiFve)
metastaFc breast cancer
What are acFve treatments for this disease?
• Postmenopausal
– Aromatase inhibitor
• Anastrazole or Letrozole (non-steroidal)
• Exemestane (steroidal)
– Aromatase inhibitor with Cell Cyclin inhibitor
• Palbociclib (Ibrance)
• Ribociclib
• Abemaciclib

13.
Letrozole and Palbociclib (Ibrance)
2015-PALOMA 1 trial showed that women with ER
+ metastaFc breast cancer who took letrozole +
palbociclib as their first treatment aYer the
diagnosis of metastaFc disease had twice as long a
response to the treatment than if they took the
letrozole alone.
2017-Does that mean they will live longer if they
start the 2 medicaFons immediately at the Fme of
diagnosis of metastaFc breast cancer?

14.
ASCO 2017

15.
PALOMA 1-FOLLOW UP 2017
Overall survival was not affected if a woman took
letrozole alone or letrozole + palbociclib at the Fme of
diagnosis of metastaFc breast cancer.
• This is probably because we have so many other medicines to
use if a woman has progression of the disease aYer first-line
therapy (whether the letrozole alone or letrozole +
palbociclib).
• BUT she may have a longer Fme before she has to change
medicines if she has letrozole + palbo as compare to letrozole
alone

16.
What does this mean for you if you have a first
metastasis of ER+ breast cancer ?
• Aromatase inhibitor alone (letrozole) may be
the best treatment for you if the disease is
“indolent” and not fast growing
• Letrozole + palbociclib might be bePer for you
if the disease is more acFve and we need a
faster response to treatment

17.
ASCO 2017
MONARCH 2 TRIAL
• ER posiFve metastaFc breast cancer
• A different cell cyclin inhibitor, abemaciclib,
and a different hormone treatment,
fulvestrant (Faslodex) in a different group of
women.

18.
ASCO 2017

19.
ASCO 2017
ER posiFve metastaFc breast cancer
A different cell cyclin inhibitor and a different hormone
treatment in a different group of women
• MONARCH 2-Good news
– The women with fulvestrant AND the new drug,
abemaciclib had less progression of their disease
at a follow up of 19 months compared to the
women with fulvestrant alone
– Will these women live longer by adding
abemaciclib to the fulvestrant?

20.
ER + breast cancer
• We have a new approach (cell cyclin
inhibiFon) and more choices to treat this
disease
• Longer Fme before we switch to
chemotherapy

21.
MetastaFc HER 2 PosiFve
breast cancer

22.
MetastaFc HER 2 posiFve breast cancer
• HercepFn (trastuzumab) is a targeted drug for
the HER 2 receptor.
• When combined with chemotherapy, it is very
acFve against metastaFc disease; not very
acFve when given alone
• How about “dual” blockade of the HER2
receptor-using 2 drugs against HER2 instead of
one drug?

23.
MetastaFc HER 2 posiFve breast cancer:
Dual blockade
• Pertuzumab + HercepFn + taxotere (Cleopatra
trial) is more acFve than HercepFn and
taxotere alone for metastaFc disease-a new
standard of care for metastaFc breast cancer
• LapaFnib (a pill) + HercepFn +chemotherapy
• NeraFnib (a pill) + HercepFn + chemotherapy

24.
MetastaFc HER 2 posiFve breast cancer:
Dual blockade: MARIANNE TRIAL
• Women with metastaFc her 2 + breast cancer
received one of these treatments as first line:
– HercepFn + taxotere or taxol
– T-DM1 (Kadcyla: hercepFn aPached to a chemo
drug, maytansine)
– T-DM1 + Pertuzumab (Perjeta)=dual blockade
• All the treatments were equal-dual blockade
was not superior-
• This does show the value of TDM-1

25.
Triple negaFve breast cancer
• All triple negaFve breast cancers are not the
same although all are ER, PR and HER 2
negaFve
• Much research on figuring this out so we can
find targets to treat
• How about immunotherapy?

26.
Triple negaFve breast cancer
• How about immunotherapy?
• Pembrolizumab (Keytruda) is acFve in some
cancers such as melanoma or lung cancer

27.
Immunotherapy has promise in metastaFc breast cancer

28.
Immunotherapy in Breast Cancer
• How do we select the right paFent?
• How do we select the right tumor?
• How do we select the right paFent with the
right tumor?

29.
BRCA mutaFon carriers with
metastaFc breast cancer
• We have an acFve new drug: Olaparib, a PARP
inhibitor

30.
BRCA mutaFon carriers with
metastaFc breast cancer

31.
BRCA mutaFon carriers with
metastaFc breast cancer

32.
Highlights of ASCO 2017
Opening new pathways
• For paFents with BRCA mutaFon
– PARP inhibitor in BRCA mutaFon carriers-aimed at
the specific problem caused by the gene mutaFon
• For paFents with ER + breast cancer:
– Cell cyclin inhibiFon – aimed at slowing down cell
growth and making cells more sensiFve to anF-
estrogen therapies

33.
Highlights of ASCO 2017
Opening new pathways
• For paFents with HER 2 + breast cancer
– Expanding on the success of HercepFn –adding
more anF-HER 2 drugs
• For paFents with Triple NegaFve breast
cancer
– Breaking the code
• Immunotherapy—just the beginning?

34.
Clinical trials at Weill Cornell Medicine

35.
Weill Cornell Breast Center Clinical Trials – Adjuvant Trials
ER+/PR+ TNBC HER2+ BRCA+
• S1207 : Phase III
Randomized, Placebo-
Controlled Clinical
Trial EvaluaFng The
Use of Adjuvant
Endocrine Therapy +/-
One Year of
Everolimus
• POSITIVE: Pregnancy
Outcome and Safety
of InterrupFng
Therapy for Women
with Endocrine
Responsive Breast
Cancer
• S1418 : A
Randomized, Phase III
Trial to Evaluate the
Efficacy and Safety of
MK-3475 as Adjuvant
Therapy for Triple
Receptor-NegaFve
Breast Cancer
• EA1131: PlaFnum
Based Chemotherapy
or ObservaFon in
TreaFng PaFents With
Residual Triple-
NegaFve Basal-Like
Breast Cancer
Following
Neoadjuvant
Chemotherapy
• NSABP B55 : A
randomized phase III
Study to access the
efficacy and safety of
olaparib versus
placebo as adjuvant
treatment in pt with
Germline BRCA1/2
mutaFons
Targeted
SupporFve
Care/
CorrelaFve/
Biobank
• Triple Nega<ve Breast
Cancer Program:
Clinical Database and
Tissue CollecFon
Project for the Study of
Breast Cancer
• Stress-Reduc<on &
Self-Healing: A Pilot
Study of Guided
MeditaFon
• Precision Medicine: To
idenFfy the frequency
and rate of acFonable
mutaFons in advanced
cancers
• Biomarkers: To idenFfy
the frequency and rate
of acFonable
mutaFons in advanced
cancers
• SCP Sa<sfac<on
Survey: PaFent and
Physician SaFsfacFon
Survey of Survivorship
Care Plans

36.
Weill Cornell Breast Center Clinical Trials – MetastaFc Trials
ER+/PR+ TNBC HER2+ BRCA+
• E2112: A Randomized
Phase III Trial of
Endocrine Therapy
plus EnFnostat/
Placebo in Men and
Women with Hormone
Receptor-PosiFve
Advanced Breast
Cancer
• IMMU-132-01: A
Phase II Study of
IMMU-132 (hRS7-
SN38 AnFbody Drug
Conjugate) in PaFents
with Epithelial Cancer
• MILLENNIUM: A Phase
1b/2 Study of
MLN0128 in
CombinaFon With
Exemestane or
Fulvestrant Therapy in
Postmenopausal
Women With ER+/
HER2- Advanced or
MetastaFc Breast
Cancer
• AAAM1906: Phase II
Trial of RuxoliFnib in
CombinaFon with
Trastuzumab in
MetastaFc HER2
PosiFve Breast Cancer
• PUMA: A Phase III Trial
of NeraFnib +
Capecitabine Versus
LapaFnib + Capecitbine
In PaFents With HER2+
MetastaFc Breast
Cancer
• Macrogenics: A Phase
3, Randomized Study
of Margetuximab Plus
Chemotherapy vs
Trastuzumab Plus
Chemotherapy in the
Treatment of PaFents
with HER2+ MetastaFc
Breast Cancer
• CELLDEX : A
Randomized
MulFcenter Pivotal
Study of CDX-011
(CR011-vcMMAE) in
PaFents with
MetastaFc, GPNMB
Over-Expressing,
Triple-NegaFve Breast
Cancer
• Rexahn: A MulF-
Center, Dose Finding,
Open Label, Phase 1
study of RX_5902 in
Subjects with
Advanced or
MetastaFc Solid
Tumors
• Oncotherapy: A Phase
I Study of OTS167PO, a
MELK inhibitor, in
PaFents with
Advanced, Triple
NegaFve Breast
Cancer
• Pharma Mar: A
MulFcenter Phase II
Clinical Trial of
PM01183 in BRCA 1/2-
Associated or
Unselected MetastaFc
Breast Cancer
Targeted
• Genentech Pathway: Open-
label Phase IIa Study
EvaluaFng Trastuzumab/
pertuzumab, ErloFnib,
Vemurafenib, and
Vismodegib in Pt's W/
Advanced Solid Tumors
With MutaFons or Gene
Expression AbnormaliFes
PredicFve of Response to
One of These Agents
• LY2157299: LY2157299
Monohydrate and
Radiotherapy in MetastaFc
Breast Cancer
• TLR7: Phase I/II study of
TLR7 agonist Imiquimod,
Cyclophosphamide, and
Radiotherapy in Breast
Cancer PaFents with Chest
Wall Recurrence or Skin
Metastases
SupporFve
Care/
CorrelaFve/
Biobank
• Triple Nega<ve Breast
Cancer Program:
Clinical Database and
Tissue CollecFon
Project for the Study of
Breast Cancer
• Stress-Reduc<on &
Self-Healing: A Pilot
Study of Guided
MeditaFon
• Precision Medicine: To
idenFfy the frequency
and rate of acFonable
mutaFons in advanced
cancers
• Biomarkers: To idenFfy
the frequency and rate
of acFonable
mutaFons in advanced
cancers
• SCP Sa<sfac<on
Survey: PaFent and
Physician SaFsfacFon
Survey of Survivorship
Care Plans

37.
The Future
The future is bright…
Our clinical trials are thriving…
Support research!
Thank you to my colleagues at the Breast Center,
Drs Andreopoulou, Cigler and Vahdat
And thank you to Dr Maura Dickler for sharing her
recent presentaFon on Highlights from ASCO