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

32s Breast Cancer—HER2/ER
602 General Poster Session (Board #9E), Sat, 8:00 AM-12:00 PM
Neoadjuvant bevacizumab (B) and trastuzumab (T) in combination with
weekly paclitaxel (P) as neoadjuvant treatment in HER2-positive breast
cancer: Results from a phase II trial (AVANTHER). Presenting Author:
Maria Fernandez Abad, Centro Integral Oncológico Clara Campal, Madrid,
Spain
Background: B in combination with T has showed meaningful activity in
patients (pts) with metastatic HER2-positive breast cancer. AVANTHER is
a Phase II trial of preoperative systemic therapy combining B with T and P
in a weekly regimen in HER2 positive breast cancer to assess safety and
efficacy of the combination. Methods: Pts with centrally-confirmed HER2positive
(IHC 3� or FISH positive) breast cancer (stage II or III including
locally advanced) received neoadjuvant chemotherapy (NC) with weekly P
(80mg/m2 /week) for 12 weeks in combination with weekly T (4mg/kg
loading dose and 2 mg/kg maintenance) and B (15mg/kg every 3 weeks) for
4 cycles. After surgery all pts received T (1 year) and liposomal doxorubicin
plus cyclophosphamide every 3 weeks (4 cycles); primary endpoint was rate
of pathological complete response (pCR) in breast and axilla. For all
patients, a tissue sample at baseline as well as at surgery was collected for
biomarker analyses. Results: A total of 44 pts have been enrolled. Median
tumor size: 3.9 cm. Seven (19.4%) pts had stage IIA; 17 (47.2%) stage
IIB; 8 (22.2%) stage IIIA and 4 (11.1%) stage IIIB. Twenty-one (58.3%)
pts had both positive-hormonal receptors and 10 (27.8%) were hormone
receptor negative. Eight (22.2%) pts had sentinel biopsy before NC, being
negative in 6 (16.7%) cases. Data from surgery (only from 36 pts): pCR was
achieved in 16 (44.4%) pts. Safety and tolerability were good, with rare
adverse events of grade �3 [1 (2.8%) episode of severe hypertension].
Conclusions: These data show that the combination of P with T and B
without an anthracycline for 12 weeks is very effective as NC in HER2
positive breast cancer pts with a high rate of pCR and minimal side effects.
604 General Poster Session (Board #9G), Sat, 8:00 AM-12:00 PM
Lapatinib in HER2� early breast cancer: Quality of life analysis. Presenting
Author: Frances Boyle, Mater Hospital, North Sydney, Australia
Background: TEACH, a randomized, double-blind, multi-center, phase III
study evaluated the efficacy and safety of 12 months lapatinib (N�1571)
versus placebo (N�1576) in women with HER2� EBC. Patients receiving
lapatinib more often reported treatment-related AEs (87% vs 47%) in the
Intent-to-treat (ITT) population. The comparison of recurrence-free survival
was not significant (p�.053). This analysis focuses on QOL in the ITT.
Methods: Participants on TEACH completed the Short Form-36 version 2
(SF-36v2) at baseline and every 6 mo. for 24 mo. SF-36v2 captures
physical, social, mental, emotional domains of patient perceptions; summary
scores of physical and mental components are derived from domain
scores using norm based scoring method. Changes in the domain and
summary scores were compared between two groups using ANCOVAs.
Missing post-baseline data were imputed using the last observation carried
forward method. A clinically relevant change in scores was defined as a 3-5
point change. Results: For randomised patients who completed the SF-36,
QOL scores decreased relative to baseline for all domains and summary
scores across all assessments and treatment arms, however the decreases
were small and not clinically meaningful. There were no statistically
significant (p� 0.05) or clinically meaningful differences between arms for
the summary scores relative to baseline (Table). Conclusions: In HER2
positive EBC one year treatment with lapatinib is associated with a
significant increase in AEs but it does not have a significant detrimental
impact on QOL when compared to placebo.
N Changes in physical summary score Changes in mental summary score
Lapatinib –
Lapatinib –
Post-baseline visit Lapatinib Placebo Lapatinib Placebo placebo (95% CI) Lapatinib Placebo placebo (95% CI)
Mo. 6 1092 1283 -0.78 -0.44 -0.33 -2.34 -1.74 -0.61
(-0.81, 0.14)
(-1.28, 0.07)
Mo. 12 1007 1204 -0.84 -0.54 -0.30 -2.74 -2.29 -0.45
(-0.84, 0.23)
(-1.16, 0.26)
Mo.6FU 983 1074 -0.53 -0.87 0.34 -2.22 -1.87 -0.35
(-0.25, 0.92)
(-1.10, 0.40)
Mo. 12 FU 940 988 -0.88 -0.82 -0.06 -3.08 -2.76 -0.31
(-0.65, 0.53)
(-1.11, 0.49)
Mo. 18 FU 834 889 -0.61 -0.89 0.27 -2.38 -2.08 -0.29
(-0.36, 0.91)
(-1.17, 0.58)
Mo. 24 FU 807 824 -0.99 -0.66 -0.33 -2.78 -3.05 0.28
(-1.00, 0.34)
(-0.61, 1.16)
Abbreviation: FU, follow-up.
603 General Poster Session (Board #9F), Sat, 8:00 AM-12:00 PM
Quantitative HER2 levels and steroid receptor expression in primary breast
cancers and in matched brain metastases. Presenting Author: Wojciech
Biernat, Medical University of Gdansk, Gdansk, Poland
Background: Breast cancer patients with HER2-positive tumors are at high
risk for brain metastases. In the current study we examined expression of
ER, PR and HER2 in primary breast tumors and in matched brain
metastases, as changes of their levels might reflect modes of escape from
therapy. Methods: Fifty-three pairs of matched formalin-fixed paraffinembedded
samples from primary breast cancers and brain metastases were
assayed for ER and PR status by immuno-histochemistry, whereas HER2
expression was quantified using the novel HERmark assay. Nuclear staining
of ER and PR �10%, and relative fluorescence of HER2 �17.8/mm2 were
considered as positive results. Results: HER2 levels in brain metastases
were generally higher than in the primary tumors (p � 3e-6), with a median
increase of 1.9-fold (range 0.08 to 199-fold). There were also substantial
differences in ER and PR status between primary tumors and brain
metastases. Loss of steroid receptor positivity in brain metastases was more
frequent than its gain (ER: 46% vs. 26%; p � 0.16; PR: 57% vs. 23%; p �
0.044). These changes resulted in a net increase in the number of
HER2-positive/ER-negative brain metastases, which more than doubled
the proportion of primary breast tumors with this phenotype (26% vs. 11%,
respectively; p � 0.08). Additionally, HER2 levels in the primary tumors
significantly correlated with overall survival when stratified by ER status (p
� 0.011). Conclusions: Brain metastases of breast cancer show significant
changes in steroid receptor status and in quantitative HER2 levels
compared to matched primary tumors. These data provide a rationale for
future studies and may help in designing treatment strategies that target
the most likely escape pathways of breast cancer.
605 General Poster Session (Board #9H), Sat, 8:00 AM-12:00 PM
A randomized phase III double-blinded placebo-controlled trial of first-line
chemotherapy and trastuzumab with or without bevacizumab for patients with
HER2/neu-overexpressing metastatic breast cancer (HER2� MBC): A trial of the
Eastern Cooperative Oncology Group (E1105). Presenting Author: Carlos L.
Arteaga, Vanderbilt University, Nashville, TN
Background: Pre-clinical and nonrandomized clinical data support synergy of the
combination of bevacizumab and trastuzumab. We conducted a randomized
double-blinded phase III trial of chemotherapy/trastuzumab � bevacizumab to
evaluate efficacy (PFS after treatment initiation) of the addition of bevacizumab
in first-line treatment of HER2� MBC. Methods: Days 1, 8 and 15 paclitaxel �
carboplatin were administered with trastuzumab and either placebo or bevacizumab
10 mg/kg every 2 weeks for a total of 6 months. Antibody therapy was
then continued without chemo every 3 weeks, until disease progression or
unacceptable toxicity. Disease assessments were performed every 3 months.
Results: Ninety-six of the planned 489 analyzable patients (pts) were accrued
between 2007 and 2009, at which time the study terminated due to poor
accrual. Seventy % of pts were post-menopausal, 60% had ER�/HER2� BC.
Median age was 55 years (28-80). Outcomes and toxicities are summarized on
the tables below. Median follow-up was 30 months. Conclusions: The combination
of chemotherapy, trastuzumab, and bevacizumab did not significantly
increased toxicity, and was overall safe and well tolerated. No significant
differences in clinical benefit were observed between both treatment arms. Data
on CTCs and Quality of Life will be presented at the meeting. This study was
conducted by the Eastern Cooperative Oncology Group (Robert L. Comis, MD,
Chair) and supported in part by Public Health Service Grants CA23318,
CA66636, CA21115, CA32291, CA31946, CA49957, CA27525, CA14548,
CA17145, CA32102, CA25224, CA49.
Outcomes Placebo (%) N�48 Bev (%) N�48
On treatment
Reason for discontinuation
Best response
PFS (# events)
Median PFS (months)
OS (# deaths)
Disease progression
Toxicity
Death
Withdrawal
Other
CR
PR
SD
PD
Not evaluable/unknown
7
60
15
0
4
12
10
42
27
13
8
34
11.1
12
9
38
21
4
4
10
10
42
19
10
18
30
12.2
14
NS
HR (0.95 CI) 0.65
(0.39-1.08) p�0.10
HR (0.95 CI) 1.23
(0.57-2.67) p�0.60
Placebo N�47 Bev N�45
Toxicity
1,2 3 4
Grade (%)
5 1,2 3 4 5
Cardiac troponin T
Hypertension
LV diastolic dysfunction
LV systolic dysfunction
Cardiomyopathy
Wound
Hemorrhage
Proteinuria
Renal failure
Thrombosis
Neutrophils
Infection
2
2
11
2
2
4
4
2
2
6
4
7
9
2
11
7
2
3
4
2
2
2
2
7
2
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