Annual Meeting Proceedings Part 1 - American Society of Clinical ...

639 General Poster Session (Board #14B), Sat, 8:00 AM-12:00 PM
Functional imaging of HER2-positive metastatic breast cancer using 64Cu DOTA-trastuzumab positron emission tomography (PET). Presenting Author:
Joanne E. Mortimer, City of Hope Cancer Center/Beckman Research
Institute, Duarte, CA
Background: We are developing 64Cu-labeled trastuzumab (tras) as a PET
imaging agent for women with HER2� beast cancer. To maximize image
quality and minimize HER2 uptake in normal tissues, we pre-administered
2 different doses of cold tras prior to injection of the imaging agent.
Methods: Pts with advanced breast cancer were eligible if they had bx
confirmed HER2 � disease, had not received anti-HER therapy for 6 mos.
and had � 1 non-hepatic site of metastasis � 2 cm outside the biopsy site.
All un-derwent staging FDG/PET and bone scan. Prior to injection of
64Cu-tras, pts. received 5 or 50 mg (2 and 4 pts) of cold tras. PET-CT was
obtained at 21-25 h and 47-48 h over fields of view chosen in reference to
18F-FDG scans. Uptake in organs and lesions were measured in terms of
body wt-normalized SUV. Lesions with intensity � adjacent tissue were
considered positive on PET. The number of metastatic sites identified on
64Cu-tras/PET was compared to the number on FDG/PET. Image quality
was assessed according to differences between the 2 pretreatment doses.
Results: Six pts have been imaged. Tras dose had a marked effect on liver
uptake of64Cu [SUV � 23�3 (mean�sd) and 6.3�0.6 for 5 and 50 mg
tras, respectively; P � 0.05]. 72 CT� lesions (32 bone, 28 nodal, 9 liver, 2
breast, 1 lung) were included in D1 and/or D2 scans. Of these, 66 of 72
(92%), 48 of 63 (76%) and 36 of 44 (82%) were detected on FDG, D1 and
D2 scans, respectively. Lesion SUVmax was 9�5(n�37, range 3-23) on D1
and 11�6 (n�27, range 1-29) on Day 2. 64Cu-tras-to-FDG SUVmax ratios
were 1.0�0.8 (range 0.2-4.3) and 1.3�1.1 (range 0.2-3.5) for D 1 and 2.
Lesion 64Cuuptake trendedliver � bone � nodes. Conclusions: 64Cu-tras/ PET visualizes HER2� lesions in bone, liver and, to a lesser degree, lymph
nodes. Pre-administration of cold tras improves the quality of tras/PET,
especially of intrahepatic lesions. In the next phase of study we will perform
64Cu-tras/PET in pts with HER2 1� and 2� disease.
641 General Poster Session (Board #14D), Sat, 8:00 AM-12:00 PM
Outcome of HER2-positive breast cancer patients following metastatic
relapse after adjuvant trastuzumab treatment since EMA regulatory approval.
Presenting Author: Jean-Philippe Spano, Groupe Hospitalier Pitié
Salpêtrière, AP-HP, Université Pierre et Marie Curie, Paris, France
Background: Trastuzumab, a humanized monoclonal antibody against
human epidermal growth factor receptor 2 (HER2) is approved in France
since 2005 for HER2-positive breast cancer patients in the adjuvant
setting. Efficacy of this treatment is clearly established but little is known
related to patient outcome if they develop metastatic relapse after adjuvant
trastuzumab. The aim of this study is to analyse these relapses with a
special focus on efficacy of anti-HER2 treatment in this setting. Methods:
We analysed 456 patients with HER2-positive early breast cancer treated
with trastuzumab containing adjuvant therapy between 2006 and 2011 in
two Departments of Medical Oncology from Université Pierre et Marie
Curie, Paris, France. Data from patients with metastatic relapse were
identified. Disease free survival (DFS) between end of trastuzumab and
relapse, quality of response, and time to progression after anti-HER2 new
treatment are reported. Results: Relapse rate was 3.3 % after adjuvant
trastuzumab (15 pts, median age 53 years, ER� 40 %). DFS between end
of trastuzumab and relapse was 244 days (95% CI: 91 - 397 days). One pt
actually had a confirmed HER2-negative metastatic disease. The other 14
pts were treated with anti-HER2 agents at relapse. On 12 evaluable pts, an
objective response was observed in 8 pts, stabilisation in 2 pts and
progression in 2 pts. Median time to progression after first line metastatic
treatment was 222 days (95% CI: 114 - 330 days). Additional data about
site of relapse and subsequent therapies are available. Conclusions:
Relapse after adjuvant trastuzumab remains a rare event in this real life
cohort of breast cancer pts. For these pts, we will present data of the
patterns of relapse and response. These data may help us to determine if
adjuvant trastuzumab has an impact on outcome of HER2 metastatic
disease compared to data in trastuzumab naive metastatic HER2-positive
breast cancer pts. We also plan to seek international collaboration to
expand our analyses, as well as overall survival.
Breast Cancer—HER2/ER
41s
640 General Poster Session (Board #14C), Sat, 8:00 AM-12:00 PM
Trastuzumab treatment in patients with advanced breast cancer (ABC) confined
to locoregional and skeletal sites: Results from a large noninterventional study.
Presenting Author: Christian Jackisch, Klinikum Offenbach, Offenbach, Germany
Background: In a prospective observation study routine trastuzumab (T) treatment
in HER2� ABC was evaluated in a total of 1,687 patients (pts) since
2001. This large number allows the subgroup analysis of patients with the
involvement of specific sites. Methods: Information on extent of advanced
disease was available in 1,674 pts (99%) with HER2 overexpressing ABC. Pts
were either pre-treated (39%) or naïve to palliative chemotherapy (CT). The
following subgroups and their characteristics were analysed: I: locally ABC only;
II: bone metastases allowing for concomitant local tumour; III: other. Results:
Locally advanced lesions were found to be the sole BC manifestation in 145 pts
(8.7%), while bone metastases � locally ABC were found in 209 pts (12.5%).
This leaves a comparative population of 1320 pts with metastases to other sites,
predominantly visceral metastases. The table shows the baseline and treatment
characteristics, as well as the long term outcome based on progression/death
observed in 79%/56% of pts. Concurrent CT (74% of total group) predominantly
consisted of a taxane (46%) or vinorelbin (24%), with no major differences
between the groups. Conclusions: In this HER2� cohort, palliative pts with local
lesions only show a comparatively high-risk profile with respect to grading,
hormone receptor status and adjuvant CT. Nevertheless, locally ABC only is a
significant favourable prognostic factor in HER2� BC treated with T combinations,
with a median survival of 4 to 5 years.
ABC subgroups
Parameter I II III
Age [median, years] 57 59 59
Age > 65 years [%] 27 26 28
Grading G3 [%] 53 46 54
Relapse-free interval [median, years] 2 2 2
Hormone receptor positive [%] 51 71 60
Local disease present [%] 100 28 30
Adjuvant CT [%] 77 57 60
Previous palliative CT [%] 26 28 42
Previous palliative hormone therapy [%] 17 38 32
> 1 year of T treatment [%] 54 58 47
Concomitant hormone therapy [%] 32 44 31
Complete remission [%] 43 12 13
Progression-free survival [median, months] 23.5 18.7 10.3
Progression-free survival rate at 2 years [%] 49 42 25
Overall survival [median, months] 57.7 45.3 30.9
642 General Poster Session (Board #14E), Sat, 8:00 AM-12:00 PM
Estrogen receptor in HER2-positive early breast cancer: Two different diseases?
Presenting Author: Eva Maria Ciruelos Gil, Medical Oncology Department,
University Hospital 12 de Octubre, Madrid, Spain
Background: HER2� breast cancer (BC) is a well characterized subtype of BC,
due to the predictive value of HER2 overexpression for anti-HER2 targeted
therapies. Nevertheless, around 50% of HER2� BC are ER� and clasiffied as
luminal B/HER2�, but their biological and clinical behaviour may be different
from HER2�/ER- tumors. Methods: We retrospectively reviewed 347 HER2�
(Herceptest ��� or FISH�) early BC patients (see Table) diagnosed at our
institution in 1997-2007, and were divided into two study groups: HER2�/ER�
(group A) and HER2�/ER- (group B). ER� was defined if expressed in � 10%
tumor cells. Results: See table below. Mean age: 54.7 y (44.6 – 65). Mean Ki 67
was higher in B (37,2 vs 22,4%, p�0.0001). At the current FU, n¼ of events
were insufficient to reach median DFS/OS. Mean DFS was 6.9 y (3.5 – 10.2);
recurrent disease was higher (p 0.003) for B (54 pts, 43%) vs A (62 pts, 28%).
5-year DFS estimates: 78.4 % (95% CI 72.3 – 83.3) and 62.3 % (95% CI 53 –
70.27) for A and B, and 10-year DFS was 73.4% (95% CI 66.6 – 79) and 52.5%
(95% CI 42.4 – 61.6) for A and B, respectively (p 0.0006). Most common
recurrent sites were local (18) and bone (9) for HER2�/ER� and liver (8) and
lung (8) for HER2�/ER-. Mean OS was 8.03y (5.4 – 10.8); 28 (12,6%) pts died
in A, vs 26 (21%) in B (p 0.043). 5-year OS estimates: 93.9 % (95% CI 89.7 –
96.4) and 87.6 % (95% CI 80.3 – 92.3) for A and B, and 10-year DFS was
84.2% (95% CI 77.5 – 89.0) and 74.1% (95% CI 63.4 – 82.2) for A and B,
respectively (p 0.01). Conclusions: ER expression in HER2� early BC defines
two clinically distinct diseases with different long-term prognosis. These data
may help to better individualize adjuvant therapies and future clinical trial
designs.
AN(%) BN(%)
N 222 125
T1
104 (47)
44 (35,2)
T2
94 (92,5)
63 (50,4)
T3
9 (4)
13 (10,4)
T4
14 (6)
5 (4)
Missing
1
N0
120 (58,5)
60 (51,2)
N1
46 (22,4)
26 (22,2)
N2
28 (13,6)
22 (18,8)
N3
11 (5,3)
9 (7,7)
Missing
17
8
Neoadjuvant CT 50 (22,5) 30 (24)
Adjuvant CT 126 (57) 88 (70,4)
Type of CT
44 (25)
30 (25,4)
No A, no T
74 (42)
57 (48,3)
A, no T
34 (19,3)
27 (23)
A and T
Other
24 (13,6)
4 (3,3)
Adjuvant RT 172 (77,4) 96 (77)
Adjuvant trastuzumab 33 (14,8) 28 (22,4)
Adjuvant HT
213 (96)
16 (13)
Tam �/- LHRHa
77 (36)
8 (50)
Aromatase inh.
136 (64)
8 (50)
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