Addition of
Bevacizumab to
Conventional Therapy
Improved PFS in
HER2-positive Breast
Cancer
Data evaluated by an
independent review
committee revealed that
the addition of
bevacizumab to
trastuzumab and
docetaxel significantly
improved PFS in
HER2-positive breast
cancer, despite findings
from an investigator
assessment that the
improvement was present
but statistically
non-significant.
Results from AVEREL, a
randomized, Phase III
trial were presented at
the 2011 CTRC–AACR San
Antonio Breast Cancer
Symposium. The trial was
designed to evaluate
bevacizumab combined
with trastuzumab and
docetaxel as 1st line
therapy for
HER2-positive, locally
recurrent/metastatic
breast cancer. Patients
had measurable or
evaluable HER2-positive,
locally recurrent/metastatic
breast cancer and
Eastern Cooperative
Oncology Group
performance status 0/1
and had not received
prior chemotherapy for
advanced disease.
Patients with central
nervous system
metastases were
excluded.
Researchers enrolled 424
patients who were
randomly assigned to
receive trastuzumab and
docetaxel (n = 208) or
to receive trastuzumab
and docetaxel plus
bevacizumab (n = 216).
At a median follow-up of
26 months, investigator
assessment revealed an
18% reduction in risk of
progression or death
with the addition of
bevacizumab compared
with that of patients
who received only
trastuzumab and
docetaxel. However, an
independent review
committee found a 28%
reduction in risk for
progression or death
with the addition of
bevacizumab. Overall,
median PFS increased by
2.8 and 2.9 months with
bevacizumab according to
investigator analysis
and independent review
committee analysis,
respectively.
Source:
SABCS 2011, Abstract No.
S4-8
Dual HER2 Blockade
Significantly Extends
PFS in HER2-positive
Breast Cancer
Adding pertuzumab to a
combination of
trastuzumab and
docetaxel chemotherapy
extended PFS by a median
of 6.1 months in
patients with metastatic
HER2-positive breast
cancer compared with
patients who received
the combination therapy
with placebo. The
findings were reported
at the 2011 CTRC–AACR
San Antonio Breast
Cancer Symposium by José
Baselga, MD, PhD,
professor in the
department of medicine
at Harvard Medical
School, associate
director of the
Massachusetts General
Hospital Cancer Center,
and chief of
hematology/oncology at
Massachusetts General
Hospital.
Researchers conducted an
international Phase III,
double-blind, randomized
trial – CLEOPATRA (CLinical
Evaluation Of Pertuzumab
And TRAstuzumab) – in
which they randomly
assigned 808 patients to
receive trastuzumab and
docetaxel chemotherapy
with pertuzumab or
placebo. PFS was 18.5
months for patients who
received pertuzumab
compared with 12.4
months for patients who
received placebo, 38%
reduction in risk for
progression. Adding
pertuzumab to the
combination therapy
resulted in an ORR
(tumor shrinkage of at
least 30%) of 80.2%
compared with 69.3% for
the combination therapy
alone. Baselga reported
69 deaths among the 402
patients treated with
the three-drug
combination and 96
deaths among the 406
patients who received
two drugs. The
three-drug combination
was safe and well
tolerated. The results
were published in the
New England Journal of
Medicine.
Source:
SABCS 2011, Abstract No.
S5-5
Exemestane plus
Everolimus Increased PFS
for Postmenopausal Women
with HR-positive
Metastatic Breast Cancer
For postmenopausal women
with hormone receptor
(HR)-positive metastatic
breast cancer, addition
of everolimus to
exemestane markedly
improved the duration of
disease control. Gabriel
N. Hortobagyi, MD, of
University of Texas MD
Anderson Cancer Center
in Houston presented
these findings from
Breast Cancer Trials of
Oral Everolimus
(BOLERO-2) at the 2011
CTRC–AACR San Antonio
Breast Cancer Symposium.
BOLERO-2, a Phase III
trial enrolled 724
postmenopausal patients
with HR-positive
metastatic breast cancer
and evidence of
progressive disease
while receiving
anastrozole or letrozole.
They randomly assigned
patients to treatment
with exemestane plus
everolimus or with
exemestane plus placebo.
Results revealed a
median progression-free
interval of 3.2 months
for 239 patients treated
with exemestane plus
placebo. Among the 485
patients treated with
exemestane plus
everolimus, researchers
found a median PFS of
7.4 months. Clinical
benefit rates, which
include complete
response, partial
response, or stable
disease exceeding 6
months, were 25.5% among
patients treated with
exemestane and placebo
and 50.5% among those
treated with exemestane
and everolimus.
Researchers were not yet
able to measure survival
analysis in BOLERO-2.
However, treatment was
well tolerated, with
oral mucositis, fatigue,
pneumonitis and
hyperglycemia being the
most common side
effects.
Source:
SABCS 2011
Zoledronic Acid Shows
Long-term Benefit in
Survivorship for
Premenopausal
ER-positive Breast
Cancer
Researchers have proven
the continuing
effectiveness of
treating patients with
estrogen receptor
(ER)-positive
premenopausal breast
cancer with adjuvant
zoledronic acid, an
intravenous
bisphosphonate, in
addition to adjuvant
endocrine treatment.
Data from the Austrian
Breast & Colorectal
Cancer Study Group
(ABCSG-12), presented by
Michael Gnant, MD, of
the Medical University
of Vienna at the 2011
CTRC–AACR San Antonio
Breast Cancer Symposium
showed that at 84 months
of follow-up, patients
were experiencing
drastically fewer
recurrences of breast
cancer and improved
rates of survivorship
without toxic side
effects.
In the four-arm trial,
researchers randomly
assigned 1,803
premenopausal patients
with early-stage,
ER-positive breast
cancer to receive
tamoxifen or anastrazole
or each of these two
treatments with
zoledronic acid for 3
years. In the initial
report, presented in
2008, Gnant and
colleagues reported
significantly improved
DFS. The most recent
long-term data, at 84
months after treatment,
revealed a 28% reduced
risk for recurrence and
a 36% reduction in risk
for death among patients
treated with zoledronic
acid. Moreover, no
patients experienced
osteonecrosis of the jaw
or renal. Researchers
also found that patients
older than 40 years with
presumed complete
ovarian blockade had a
34% reduced risk for
recurrence and a 44%
reduced risk for death.
According to the
researchers, these data
suggest that adding
zoledronic acid to
adjuvant endocrine
therapy including
ovarian function
suppression should be
considered for
premenopausal women with
ER-positive, early
breast cancer.
Source:
SABCS 2011,
Abstract No. S1-2
Zoledronic Acid use with
Endocrine Therapy Increased Bone
Mineral Density and Reduced Risk
for Disease Recurrence in
Postmenopausal Early Breast
Cancer
The addition of
zoledronic acid to
adjuvant endocrine
therapy increased bone
mineral density and
reduced the risk for
disease recurrence among
postmenopausal women
with early HR-positive
breast cancer, according
to new data from the
Zometa-Femara Adjuvant
Synergy Trial (ZO-FAST)
presented at the 2011
CTRC–AACR San Antonio
Breast Cancer Symposium.
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Richard de Boer, MD, of the Royal Melbourne Hospital in
Victoria, Australia, and colleagues explored adding
zoledronic acid to adjuvant endocrine therapy to reduce
bone mineral density loss seen with aromatase inhibitors
and to improve survival outcomes.
Researchers randomly assigned 1,065 patients who were
about to commence letrozole, an aromatase inhibitor, to
receive immediate zoledronic acid every 6 months or to a
delayed group where zoledronic acid was started at a
later time only if the patient experienced a fracture or
a documented fall in bone mineral density. After 60
months of follow-up, the primary endpoint of the trial
was successfully achieved—up-front zoledronic acid
significantly decreased bone mineral density loss in
both the lumbar spine and the hip. The secondary
endpoint of an improvement DFS was also met, with a 34%
decrease in disease recurrence in patients receiving the
up-front zoledronic acid.
Researchers conducted an exploratory subgroup analysis
based on menopausal status at the time of breast cancer
diagnosis. Data indicated that in women who were truly
menopausal at diagnosis, immediate treatment with
zoledronic acid reduced the risk for disease recurrence
by 29% and improved OS by 35%. Researchers pointed out
that additional studies are needed to fully define the
patient populations most likely to benefit from adjuvant
zoledronic acid in this setting. According to the
researchers, until then, patients with HR-positive
breast cancer who are postmenopausal and about to
commence letrozole have the option of considering the
addition of zoledronic acid, primarily to maintain bone
mineral density but also with the aim of reducing the
risk for disease recurrence.
Source:
SABCS
2011, Abstract No. S 1-3
Clodronate Appeared
Safe, Modestly Affected
Breast Cancer Disease
Events
The results of B-34 – a
prospective, randomized,
double-blind, Phase III clinical
trial – presented at the 2011
CTRC–AACR San Antonio Breast
Cancer Symposium revealed that
the bisphosphonate – clodronate
– had a low incidence of AEs and
toxicity among patients with
breast cancer and may modestly
reduce the incidence of distant
metastases in postmenopausal
women. These findings were
presented by Alexander H. G.
Paterson, MD, professor in the
departments of medicine and
oncology at the University of
Calgary in Canada.
Paterson and his colleagues enrolled 3,323 patients with
stage I, II, or III breast cancer between January 22,
2001, and March 31, 2004. Data were presented on 3,311
patients (99.6%) with follow-up information. Slightly
more than 75% of the patients had pathologically
negative axillary nodes, 64% were 50 years or older at
entry, and 22% had ER-negative or progesterone receptor
(PgR)–negative breast cancer. Researchers randomly
assigned patients to receive 3 years of clodronate or an
oral placebo three times a day. In addition, patients
also underwent surgery (lumpectomies or mastectomies)
and received radiation therapy and chemotherapy or
hormonal therapy. Median follow-up for patients who were
still alive was 7.6 years. A total of 598 patients
experienced disease events, defined as any cancer
(either recurrent breast cancer or a new primary) or
death (cancer-related or otherwise): 286 in the
clodronate group and 312 in the placebo group. The
relative reduction of events in the clodronate group was
~9% compared with the placebo group, which was not
statistically significant.
Researchers observed a 16% relative reduction in
mortality in the clodronate group. They also observed
relative reductions of 23% and 26% in the clodronate
group for the occurrence of skeletal and non-skeletal
metastases, respectively. Results also demonstrated that
clodronate might perform better in patients 50 years or
older when diagnosed with breast cancer and for women
with ER/PgR-positive nodes. Clodronate was generally
tolerable, and the toxicities observed were mainly due
to concomitant systemic chemotherapy, according to the
researchers.
Source:
SABCS 2011,
Abstract No. S 2-3
New Test Predicts
Risk for Recurrence for
Patients with DCIS
In a significant advance
for patients with ductal
carcinoma in situ (DCIS),
researchers have
developed and
prospectively validated
a multigene test to
identify the risk for
recurrence of breast
cancer. The method
combines measuring tumor
gene expression with a
gene expression
algorithm to decipher
the genetic
underpinnings of a
patient’s cancer and
determine whether the
individual patient
should be treated with
surgery (usually
lumpectomy) or a
combination of surgery
and radiation. This is
the first time a
multigene test has been
used to differentiate
lower-risk and more
aggressive forms of DCIS
and will allow
physicians to spare many
patients the need to
undergo radiation.
Lawrence J. Solin, MD,
of Einstein Medical
Center in Philadelphia,
presented these results
at the 2011 CTRC–AACR
San Antonio Breast
Cancer Symposium.
The validation study of
the DCIS score was a
collaboration among the
Eastern Cooperative
Oncology Group (ECOG),
North Central Cancer
Treatment Group, and
Genomic Health. The
validation utilized
patient tumor samples
from E5194, an ECOG-led,
multi-institutional
study of patients with
low-, intermediate-, or
high-grade DCIS who had
been treated surgically
but had not received
radiation. E5194 was the
first prospective study
of local excision alone
for DCIS, and its 5-year
results were reported at
SABCS in 2006.
Researchers tested and
scored tumors from 327
patients to determine
their risk for
recurrence. The DCIS
validation study team
used the Oncotype DX
breast cancer assay,
which has been available
for invasive breast
cancer since 2004, and a
DCIS score algorithm to
study these tumor
samples. The test uses
RT-PCR, which
quantitates the level of
RNA in the individual
tumor sample to reveal
its underlying biology.
The level of RNA is then
used by a prespecified
algorithm to calculate a
DCIS score, which
predicts the likelihood
of local recurrence,
defined as either the
development of a new
invasive breast cancer
or the recurrence of
DCIS. Solin also
reported 10-year results
of E5194, in which 46
patients had an
ipsilateral breast event
(IBE; defined as
ipsilateral local
recurrence of DCIS or
invasive cancer) at a
median follow-up of 8.8
years. Continuous DCIS
score was significantly
associated with IBE when
adjusted for tamoxifen
use and provided value
beyond the traditional
measures of tumor size,
tumor grade, and margin
status. Numerous
studies, including the
current study, have
shown that routine,
microscopic pathology
grading is not a
reliable indicator of
the risk for recurrence.
According to
researchers, the DCIS
score will help
physicians understand
the underlying biology
of DCIS for an
individual patient and
accurately gauge the
risk for that person. As
a result, the patient
and physician can decide
on the appropriate
course of treatment
based on a more complete
understanding of the
risk involved.
Source:
SABCS
2011, Abstract No. S 4-6
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