Clinical challenges in management of her 2 positive by gladwell kiarie

Images are not actual patients.
Dr. Gladwell G Kiarie
Medical Oncologist
Senior Lecturer University of Nairobi

Nairobi Cancer Registry, KEMRI
Kenya estimates
(GLOBOCAN) 2012
Cervix Cancer
New cases: 4,802
No. of Deaths: 2,451
Age Standardized Incidence
rates: 40.5/100,000
Breast Cancer
New cases: 4,465
No. of Deaths: 1,969
Age Standardized Incidence
rates 38.6/100,000
Oesophagus
New cases: 1,560
Deaths: 1,428
Age Standardized
Incidence rates 15.1/100,000
Number of cases

Local Hormone Receptor Status
Her-2/neu positivity 20.26% 31%
Her 2/new borderline 27.8%
ER+ PR+ HER2+ 6.33% 11.9%
ER- PR – HER 2 – 28% 17%
ER- PR- HER 2 + 12.7% 10.2%
ER+ PR + HER2 – 20.3% 12%
*(Anal Quant Cytol Histol, April 2006; 28 (2):97-103.
* Unpublished data
In our study (66.9%) did the endocrine test while (65%)
did the HER 2 test.

Case 1
68 yr old retired nurse known HTN
Thyroidectomy in 1990
Nipple excoriation and some discharge, itching and
tingling.
No palpable lump on breast or axilla
Mammogram: skin and areola thickening, nipple
retraction, subareolar and diffuse microcalcification.
No discrete mass seen.

Histology report Case 1
Core biopsy:
Staging
Mastectomy and Axillary node sampling:
 Pagets Disease
 DCIS grade 3
 Invasive ductal carcinoma below the nipple
Margins clear
 Lymph nodes negative (0/3)
 ER neg, PR neg and HER 2 pos (3 +)

Discussion Points
Staging : Bone Scan? PET CT Scan
Radiation first?
Adjuvant Chemotherapy (node negative)
Herceptin : same period

APT Study: Phase II Study of Paclitaxel + Trastuzumab as
Adjuvant Therapy for Small, Node-negative HER2+ Breast
Cancer
Tolaney SM et al, SABCS 2013, abstract #S1-04
 Randomized adjuvant HER2+ trials included few small, lymph
node negative breast cancers
 Patients: 406 pts with node-negative, HER2+ breast cancer, < 3
cm
 2/3 ER+, 20% < 0.5 cm
 Treatment: Paclitaxel and trastuzumab weekly x 12, followed
by 9 months of single agent trastuzumab
 Results: 3.6 years median follow-up
 10 recurrences/deaths (2.5%): 2 distant, 4 locoregional, 3
contralateral breast cancers, 1 non-breast cancer death
(ovarian ca)
 3 year DFS 98.7%

APT Study: Phase II Study of Paclitaxel + Trastuzumab as
Adjuvant Therapy for Small, Node-negative HER2+ Breast
Cancer
Tolaney SM et al, SABCS 2013, abstract #S1-04
Toxicity:
2 symptomatic CHF (resolved on stopping trastuzumab)
13 asymptomatic declines in LVEF (able to resume
trastuzumab in 11)
Conclusion: Paclitaxel plus trastuzumab can be considered
a reasonable approach for majority of patients with small,
lymph node negative, HER2+ breast cancer

Case 2
JO 36 yr old civil servant.
Pregnant 16 weeks with a BOH. She is a sickler who
had lost a baby the previous year to sickle cell.
Breast lump on the left breast with palpable axillary
nodes.
Core biopsy: grade 3 IDC ER negative PR negative
HER 2 positive (3 +)
Cardiac evaluation normal.

Management Case 2
Staging Tests done Abd/ Pelvic ultrasound
Surgery : Lumpectomy was done
Chemotherapy
Delivered a bouncing baby boy weighing 3.2kg
Completion mastectomy?
Radiation
Tamoxifen and Herceptin

Trastuzumab in Pregnancy
The majority of the women exposed to trastuzumab
developed oligo- or anhydraminos, and increases in
amniotic fluid were observed when the drug is
discontinued.
?directly causes a decrease in amniotic fluid,
?role of epidermal growth factor receptor (EGFR) in fetal
kidney development.
Does Trastuzumab crosses the placenta?
direct evidence from humans is lacking,
maternal-placental transfer of immunoglobulin-G1
antibodies such as rituximab occurs,
studies in cynomologus monkeys show placental transfer of
trastuzumab during early and late gestation.

Trastuzumab in CNS Disease
 Brain Metastasis:
 Trastuzumab (Herceptin),
 Lapatinib (Tykerb),
 Pertuzumab (Perjeta
 Ado-trastuzumab emtansine (Kadcyla) (T-DM1).
 These drugs are not usually able to reach the brain
as easily as they can reach the rest of the body, with
lapatinib being a possible exception.
 Therefore, when cancer spreads to the brain it is
usually treated with surgery and/or radiation
therapy.

Brain Metastasis in HER 2 positive
Disease
1. Surgery for single brain metastasis if the metastasis is > 3 to 4 cm or
if there is evidence of symptomatic mass effect.
2. Single brain metastasis < 3 to 4 cm without symptomatic mass effect
: stereotactic radiosurgery or surgical resection, depending on the
location and surgical accessibility of the tumor, need for tissue
diagnosis, and other considerations, such as medical risk factors for
surgery and patient preference.
3. Surgical resection, with postoperative radiotherapy to the resection
bed to reduce the risk of local recurrence.
4. Single brain metastasis > 3 to 4 cm that is deemed unresectable and
unsuitable for stereotactic radiosurgery, clinicians may discuss the
options of whole-brain radiotherapy or fractionated stereotactic
radiotherapy.
5. After treatment, serial imaging every 2 to 4 months may be used to
monitor for local and distant brain failure.

Cardiotoxicity with Herceptin
 Trastuzumab causes a form of cardiotoxicity not
dose-dependent, and ultrastructural changes typical
of anthracycline therapy are not seen on cardiac
biopsy specimens;
 Cardiac dysfunction, is reversible in 60% of cases,
and full LVEF recovery.
 TNI measurement during trastuzumab therapy
allows for identification of patients at risk of
cardiotoxicity as well as of those who, despite HF
therapy, will not recover from cardiac dysfunction.

Cardiotoxicity cont’d
Troponin I (TNI) is an early marker of myocardial
injury, with high diagnostic and high prognostic
TNI increase has been shown to predict LVEF
reduction and associated adverse cardiac events. The
role of TNI in trastuzumab-treated patients has never
been investigated.

Time of the first detection of elevated troponin value.
Cardinale D et al. JCO 2010;28:3910-3916
©2010 by American Society of Clinical Oncology

(A) Kaplan-Meier curve of time to first cardiac event in patients developing trastuzumab-induced
cardiotoxicity (TIC) and in patients who did not (No TIC).
Cardinale D et al. JCO 2010;28:3910-3916
©2010 by American Society of Clinical Oncology

HER-2 Oncogene: amplified and overexpressed in 20-25%
HER-2 Over-Expressing Breast Cancer
18
cancer cell
Pertuzumab
Anti-HER-2
Antibody
cell division
HER-2
nucleus
Trastuzumab
Anti-HER-2 Antibody
of breast cancer
Lapatinib
Dual HER-1/HER-2
Tyrosine Kinase Inhibitor
T-DM1
Antibody-Drug
Conjugate

After Resistance to HER 2
inhibition

Metastatic Breast Cancer
Pertuzumab + trastuzumab + taxane
Endochrine therapy + trastuzumab
2nd line: Trastuzumab + TDMI
3rd line: TDMI, pertuzumab, lapatinib and xeloda
?resistance

The Concept of Trastuzumab Resistance
Definition of “trastuzumab resistance”
No clear clinical definition
 Described in terms of disease progression or recurrence on/after
trastuzumab
 Observed eventually in almost all HER2+ metastatic
cancers1,2
Mechanisms contributing to such disease progression
Strategies to overcome these resistance mechanisms
1. Wong AL and Lee SC. Int J Breast Cancer. 2012;2012:415170. doi: 10.1155/2012/415170;
2. Arribas J, et al. Cancer Res. 2011;71(5):1515-1519.

Trastuzumab
benefit
Trial B31/Trial N9831
ACPT
N
ACP
ACPT 1672 96
ACP 1679 193
HR = 0.47, P < .0001
0 1 2 3 4 5
100
90
80
70
60
50
Years From Randomization
Reprinted from Romond EH, et al. NEJM. 2005;353(16):1673-1684.
Copyright © 2005 Massachusetts Medical Society. All rights reserved.
90.4% 89.7%
81.5%
73.7%
? Trastuzumab-resistant
? No benefit
from
trastuzumab
Events

HER2
Alterations in
downstream molecules:
•Increased Akt signaling
•PTEN deficiency
•p27kip1 downregulation
Disrupted antibody-receptor
interaction:
•MUC-4
•HER2 mutations
Increased receptor signaling:
•HER family members
•Increased ligands
•IGF-IR signaling/receptor crosstalk
Based on Bailey TA, et al. J Carcinog. 2011;10(1):28.

Emerging Therapies
Receptor level agents
Pertuzumab + trastuzumab
Lapatinib + trastuzumab
HER2-specific tyrosine kinase inhibitors
 Neratinib
 Afatinib
Downstream effectors
mTOR inhibitors
 Everolimus

p85
G1
S
Translation
(cyclin D1)
++
LAP
Emerging data support co-targeting the HER2 pathway in
trastuzumab-resistant cancers
Based on Bailey TA, et al. J Carcinog. 2011;10(1):28.
NER/AFAT

Existing Strategies for Treatment of HER2+ Breast
Cancer Progressing On/After Trastuzumab
Lapatinib1-3
Approved in combination with capecitabine
Continuation of trastuzumab1-3
Retrospective and prospective studies demonstrate that
continuing trastuzumab provides superior
clinical benefit1,2
T-DM13-5
Approved as monotherapy in 2013 based on EMILIA
 Additional recent data from TH3RESA6
1. Wong AL and Lee SC. Int J Breast Cancer. 2012;2012:415170. doi: 10.1155/2012/415170;
2. Gajria D and Chandarlapaty S. Expert Rev Anticancer Ther. 2011;11(2):263-275;
3. Jelovac D and Emens LA. Oncology (Williston Park). 2013;27(3):166-175. 4. Barginear MF, et al. Mol Med. 2013;18:1473-1479; 5.
KADCYLA [package insert]. South San Francisco, CA: Genentech, Inc; 2013. Available at:
http://www.gene.com/download/pdf/kadcyla_prescribing.pdf; 6. Wildiers H. ECCO-ESMO 2013. Abstract 15.

Median, months No. events
PFS by Investigator Assessment
0 2 4 6 8 10 12 T1im4e, m1o6
CAP + LAP 6.4 304
Progression-free survival, %
T-DM1 495 404
419
Reprinted from Verma S, et al. NEJM. 2012;367(19):1783-1791.
Copyright © 2012 Massachusetts Medical Society. All rights reserved. T-DM1 9.6 Images 265 are not actual patients.
27
CAP+ LAP
No. at risk by independent review:
18 20 22 24 26 28 30
496
310
341
176
236
100
129
183
73
130
53
101
35
72
25
54
14
44
9
30
8
18
5
9
1
3
01
00
80
60
40
20
0
Stratified HR = 0.65 (95% CI, 0.55, 0.77) P < .001
1:1
HER2+ (central) LABC
or MBC (N = 991)
•Prior taxane and
trastuzumab
•Progression on
metastatic tx or within 6
mo of adjuvant tx
PD
TT--DDMM11
33..66 mmgg//kkgg qq33ww IIVV
Capecitabine
1000 mg/m2 orally bid, days 1–14, q3w
+
Lapatinib
1250 mg/day orally qd
PD

TH3RESA: T-DM1 Improved PFS Versus Physician’s Treatment of
Choice for HER2+ mBC
• Treatment continued until disease progression or intolerable toxicity
• Estimated completion date: June 2015
N ~ 600
•Locally advanced or
metastatic HER2+ breast
cancer
•Prior Trastuzumab, taxane,
and lapatinib
•Disease progression after
≥2 regimens HER2-directed
therapy in metastatic/
recurrent setting
TT--DDMM11 ((33..66 mmgg//kkgg))
eevveerryy 2211 ddaayyss
Treatment of
physician’s choice
R2
:1
Key endpoints:
• Primary: PFS by
investigator
assessment per
RECIST, OS
• Secondary: ORR
UNPUBLISHED DATA REMOVED
Median follow-up: Treatment of Physician’s Choice (TPC), 6.5 months; T-DM1, 7.2 months. Unstratified HR = 0 (P < 0.0001).
Wildiers H. ECCO-ESMO 2013. Abstract #15.

Trastuzumab: 44 mmgg//kkgg llooaadd  22 mmgg//kkgg qqww oorr 88 mmgg//kkgg llooaadd  66 mmgg//kkgg qq33ww
PPeerrttuuzzuummaabb:: 884400 mmgg llooaadd  442200 mmgg qq33ww
N = 66
• HER2+
(HercepTest)1,2
• Progressed on
trastuzumab-based
therapy as most
recent treatment
Primary endpoint:
Overall response rate and/or CBR
Secondary endpoints include:
•Safety
•Duration of response
•Time to response
•TTP
•PFS
Median PFS: 5.5 mo
Response Patients (N = 66)
CR 7.6%
PR 16.7%
SD ≥ 6 mo 25.8%
ORR 24.2%
CBR 50%
1. Baselga J, et al. JCO. 2010;28(7):1138-1144; 2. Birner P, et al. CCR. 2001;7(6):1669-1675.

L + T
(n = 146)
(n = 145)
113 (78) 105 (72)
9.5 14
Died, n (%)
Median, months
HR (95% CI)
Log-rank P .026
0.74 (0.57 to 0.97)
Lapatinib (1500 mg/day PO)
(n = 148)
Lapatinib (1000 mg/day PO) +
Trastuzumab
(4 mg/kg load  2 mg/kg weekly)
(n = 148)
N = 296
• HER2+ (FISH+/IHC 3+)
• Progressed on most recent
trastuzumab regimen
• Prior anthracycline- and
taxane-based regimens
Primary endpoint:
Progression-free survival: Investigator
•Overall survival
•Overall response rate
•Clinical benefit rate
•Quality of life
•Safety
Crossover if PD after 4 wk therapy (N = 73)
RANDOMIZE
Schematic based on data from Blackwell KL, et al. JCO. 2010;28(7):1124-1130.
Figure reprinted from Blackwell KL, et al. JCO. 2012;30(21):2585-2592.
Copyright © 2012 American Society of Clinical Oncology. All rights reserved.
70%
6-month OS
L + T
L
Overall Survival, %
No. at risk
L + T
L
80%
56%
41%
12-month OS
L
Time Since Random Assignment, months
100
80
60
40
20
5 10 15 20 25 30 35
0
0
146 120 87 63 42 25 1
145 100 64 46 28 13

Neratinib ((224400 mmgg//ddaayy PPOO))
PPrriioorr ttrraassttuuzzuummaabb ttrreeaattmmeenntt
((nn == 6666))
NNeerraattiinniibb ((224400 mmgg//ddaayy PPOO))
NNoo pprriioorr ttrraassttuuzzuummaabb ttrreeaattmmeenntt
((nn == 7700))
N = 136
• HER2+ (FISH+)
• Prior cytotoxic and
trastuzumab-based
regimens
a Confirmed response.
b Exact CIs were constructed.
c CR + PR + stable disease ≥ 24 weeks.
Burstein HJ, et al. JCO. 2010;28(8):1301-1307.
RANDOMIZ
E
Clinical Activity Prior T
N = 63
No Prior T
N = 64
16-wk PFS rate (95% CI) 59% (45 to 71) 78% (66 to 87)
Median PFS, wk (95% CI) 22.3 (15.9 to 31.6) 39.6 (31.0 to 55.1)
Objective response rate, %a (95% CI)b 24 (14-36) 56 (43-69)
Stable disease time, %
<24 weeks
33
20
≥24 weeks
10
13
Clinical benefit rate, %c (95% CI)b 33 (22-46) 69 (56-80)

N = 45
•HER2+ ABC
•Progression on
prior trastuzumab
Neratinib (240 mg/day)
+ TRAS (2 mg/kg/wk)
Phase 1: Dose Escalation (N = 8)
+ TRAS (2 mg/kg/wk)a
n = 4
+ TRAS (2 mg/kg/wk)a
n = 4
Phase 2 (N = 37)
Clinical Activity N = 33b
Objective response rate, % (95% CI) 27 (13-46)
16-week progression-free survival rate, % (95% CI) 47 (29-63)
Median PFS, weeks (95% CI) 19 (15-32)
a Following a loading dose of 4 mg/kg.
b Evaluable for efficacy (phase 2).
Swaby R, et al. ASCO 2009, Abst 1004 (abstract).
OR
No dose-limiting toxicities observed

Phase 2 Trial: Afatinib Monotherapy in
Heavily Pretreated HER2+ MBC Progressing
After Trastuzumab
N = 41
•HER2+ (IHC2+/FISH+)
•Progression on prior
trastuzumab or
trastuzumab-based
chemotherapy
Afatinib (50 mg/day)
Best Response
(RECIST)
Lin NU, et al. BCRT. 2012;133:1057-1065.
Median PFS: 15.1 weeks
Median OS: 61.0 weeks
All treated
Patients, %
(N = 41)
Evaluable
Patients, %a
(N = 35)
Median duration,
weeks
(range)
CBR (CR + PR + SD) 46 54 17.1 (7.3-64.0)
PR 10 11 12.0 (7.4-56.1)
Stable disease 37 43 –
Progressive disease 39 46 –

Phase 3 Trial: Trastuzumab + Vinorelbine ± Everolimus in Heavily
Pretreated MBC Following Progression on Trastuzumab (BOLERO-3)
Placebo (PO daily) +
Vinorelbine (25 mg/m2
weekly) + TRAS (2 mg/kg
N = 572a
•Locally advanced or metastatic
HER2+ breast cancer
•Prior taxane required
•TRAS resistance
–Adjuvant: progression on or within 12 months of
TRAS
–Metastatic: progression within 4 weeks
of TRAS
•Measurable disease only
a Actual enrollment was 569.
b Following a 4-mg/kg loading dose on day 1, cycle 1 (1 cycle = every 21 days).
O’Regan RM, et al. ASCO 2013, Abst 505 (oral presentation).
Everolimus (5 mg PO daily) +
Vinorelbine (25 mg/m2 weekly)
+ TRAS (2 mg/kg weeklyb)
(n = 284)
weeklyb)
(n = 285)
Therapy until progressive disease
or intolerable toxicity
RANDOMIZE
1:1
• Stratification by prior lapatinib use (yes/no)
Primary endpoint:
Progression-free survival
•Overall survival
•Overall response rate
•Time to deterioration of ECOG PS
•Safety
•Duration of response
•Clinical benefit rate
•Quality of life

HER2-Positive Breast Cancers Are Intrinsically Resistant to
Endocrine Therapy
Transfection of ER+ breast cancer cells with HER2 renders
them resistant to tamoxifen1
Retrospective analyses of trials in the ER+ metastatic
setting show a worse outcome for cancers that co-express
HER2 compared to those that do not2
Median progression-free survival is less than
6 months for ER+, HER2+ MBC treated with aromatase
inhibitors3,4
1. Benz CC, et al. BCRT. 1992;24(2):85-95; 2. De Laurentiis M, et al. CCR. 2005;11(13):4741-4748; 3. Kaufman B, et al. JCO.
2009;27(33):5529-5537; 4. Johnston S, et al. JCO. 2009;27(33):5538-5546.

HER2– HER2+/–
Reprinted from Nahta R and O’Regan R. BCRT. 2012;135(1):39-48.

But is this true for all ER+, HER2+ breast cancers?
HER2
ER

T L T/L T L T/L T L T/L T L T P T/P T/P T/L
PTX PTXFEC FECPTX D ECD Percent PCR
Nahta R and O’Regan R. BCRT. 2012;135(1):39-48.

UNPUBLISHED DATA
Hazard ratio = 5.24 (95% CI, 2.25-12.1)
P < .001 log-rank test
Hazard ratio = 0.88 (95% CI, 0.38-2.06)
P = .775 log-rank test
ER-negative, HER2-positive
DFS
ER-positive, HER2-positive
DFS
REMOVED
Reprinted from von Minckwitz G, et al. SABCS 2011, Abst S3-2 [presentation].

Why Is This Important?
We may be (and probably are) over-treating a subgroup
of ER+, HER2+ breast cancers in the (neo)adjuvant setting
This subgroup of patients with ER+, HER2+ breast cancers
may suffer late recurrences (similar to what we see with
luminal A cancers)

HER2+/ER–
HER2+/ER+
HER2+/ER+++
Percent PCR
ER expression
1. Bhargava R, et al. Mod Pathol. 2011;24(3):367-374; 2. Reprinted from Nahta R and O’Regan R. BCRT. 2012;135(1):39-48.

Distant Disease-Free Survival
Good prognosis
Poor prognosis
100
Percent survival
100
Percent survival
80
60
40
20
0
Breast Cancer-Specific Survival
Good prognosis
Poor prognosis
Log-rank (Mantel–Cox) test Log-rank (Mantel–Cox) test
P value 0.0170 0.0523
80
60
40
20
0
2 4 6 8 10 0 2 4 6 8 10
Time, years
0
Time, years
P value
Images are not Reprinted from Knauer M, et al. British J Cancer. 2010;103(12):1788-1793. actual patients.

Bi-Directional Crosstalk Between
ER and HER2
Signaling through EGFR family including HER2
downregulates ER1,2
Conversely, inhibition of HER with trastuzumab or
lapatinib increases signaling through ER3,4
ER signaling is increased in HER2-positive cell lines that
are resistant to HER2-directed agents4,5
HER2 expression and activity are increased in hormone-resistant
cancers, compared with
hormone-sensitive cancers6,7
1. Pinzone JJ, et al. Mol Cell Biol. 2004;24(11):4605-4612; 2. Stoica A, et al. J Endocrinol. 2000;165(2):371-378;
3. Sabnis G, et al. Cancer Res. 2009;69(4):1416-1428; 4. Xia W, et al, Proc Natl Acad Sci. 2006;103(20):7795-7800;
5. Valabrega G, et al. Oncogene. 2005;24(18):3002-3010; 6. Gee JM, et al. Endocr Relat Cancer. 2005;12(Suppl 1):S99-S111; 7. Johnston SR. CCR.
2005;11(2 Pt 2):889s-889s.

HER2 HER1/2/3
ERER
ERE
PI3-K
AKT
FOXO3a
Membrane
FOXO3a
ER-regulated
gene
transcription x
Ras
MEK
Erk1/2
Nucleus
Cytoplasm
HER2 HER1/2/3
FOXO3a
ERER
ERE
PI3-K
AKT
ER-regulated
gene
transcription
Ras
MEK
Erk1/2
Cytoplasm
Nucleus
Membrane
TTKKII xx
TTRRAASSTT
1. Xia W, et al. Proc Natl Acad Sci. 2006;103(20):7795-7800; 2. Valabrega G, et al. Oncogene. 2005;24(18):3002-3010; 3. Reprinted from Nahta
R and O’Regan R. BCRT. 2012;135(1):39-48.

Clinical Relevance of This Crosstalk
 Inhibition of HER2 without inhibition of ER may
increase ER signaling, allowing ER to act as an escape
mechanism
 This could contribute to the lower PCR seen in ER+, HER2+
breast cancers in the neoadjuvant setting, and this could
have potential implications in the metastatic setting
 Potential reason for smaller PFS benefit observed in ER+, HER2+
versus ER–, HER2+ subsets in BOLERO-3?
 There may be a subset of ER+, HER2+ breast cancers where
ER inhibition is critical
 A few patients demonstrated a change from ER– to ER+
following trastuzumab-based chemotherapy
Mittendorf EA, et al. CCR. 2009;15(23):7381-7388.

Role of ER in Trastuzumab Resistance
 Although HER2 signaling is associated with intrinsic
resistance to endocrine agents, a subset of HER2+,
ER+ cancers appears to be driven, at least in part,
by ER
 Identification of these cancers is crucial
 They may require less aggressive treatment
approaches with earlier institution of ER inhibition
 They may behave like ER+, HER2– cancers with late
relapses
 ER plays a role in resistance to HER2-directed
agents

HHEERR22 TThheerraappyy CCoommbbiinnaattiioonnss
NNeeoo AALLTTTTOO:: PPrreeoopp HHEERR22++
BBaasseellggaa JJ eett aall,, LLaanncceett 337799::663333--664400,, 22001122
Invasive, operable
HER2+ breast
cancer
T > 2 cm
N=450
llaappaattiinniibb
ttrraassttuuzzuummaabb
llaappaattiinniibb
FE
C
X
3
S
U
R
G
E
R
Y
R
A
N
D
O
M
I
Z
E
LLaappaattiinniibb 11550000 mmgg//dd
ppaacclliittaaxxeell
8800 mmgg//mm22
TTrraassttuuzzuummaabb wweeeekkllyy
LLaappaattiinniibb 11000000 ttoo 775500
pCR

Neo ALTTO: Survival Follow-up Analysis
Piccart M et al, SABCS 2013 abstract #S1-01
LLaappaattaanniibb ++
TTrraassttuuzzuummaabb
TTrraassttuuzzuummaabb LLaappaattiinniibb
3 yr EFS (all) 84% 78% 78%
HR+ 83% 80% 86%
HR- 86% 72% 70%
3 yr OS (all) 95% 90% 93%
HR+ 97% 94% 93%
HR- 93% 87% 93%
NNoonnee ssttaattiissttiiccaallllyy ssiiggnniiffiiccaanntt

Neo ALTTO Survival Follow-up
Analysis: Conclusions
 Underpowered to detect moderate EFS and OS
differences, await results of ALTTO adjuvant trial
 Patients who achieved pCR hhaadd ssiiggnniiffiiccaannttllyy bbeetttteerr EEFFSS
aanndd OOSS ccoommppaarreedd wwiitthh nnoo ppCCRR
• HER2+/ER- disease different from HER2/ER+ disease

Conclusion
“In the management of patients with breast cancer,
selecting the most efficacious therapy remains a
challenging but achievable goal. Improved
understanding of the targets for therapy has made
possible an unprecedented level of insight into the
individual patient’s cancer genome and biology.
Concurrent development of predictive biomarkers
along with targeted therapies is the new paradigm for
achieving optimal care and sparing patients
unnecessary toxicity and expense”.

Clinical challenges in management of her 2 positive by gladwell kiarie

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