Nature Communications,
Journal Year:
2023,
Volume and Issue:
14(1)
Published: June 7, 2023
DESTINY-CRC01
(NCT03384940)
was
a
multicenter,
open-label,
phase
2
trial
assessing
the
efficacy
and
safety
of
trastuzumab
deruxtecan
(T-DXd)
in
patients
with
HER2-expressing
metastatic
colorectal
cancer
(mCRC)
that
progressed
after
≥2
prior
regimens;
results
primary
analysis
are
published.
Patients
received
T-DXd
6.4
mg/kg
every
3
weeks
were
assigned
to
either:
cohort
A
(HER2-positive,
immunohistochemistry
[IHC]
3+
or
IHC
2+/in
situ
hybridization
[ISH]+),
B
(IHC
2+/ISH-),
C
1+).
Primary
endpoint
objective
response
rate
(ORR)
by
independent
central
review
A.
Secondary
endpoints
included
ORR
(cohorts
C),
duration
response,
disease
control
rate,
progression-free
survival,
overall
pharmacokinetics,
T-DXd.
86
enrolled
(53
A,
15
B,
18
C).
Results
published,
reporting
an
45.3%
Here,
we
report
final
results.
No
responses
occurred
cohorts
C.
Median
6.9,
15.5,
7.0
months,
respectively.
Overall
serum
exposure
(cycle
1)
T-DXd,
total
anti-HER2
antibody,
DXd
similar
regardless
HER2
status.
Most
common
grade
≥3
treatment-emergent
adverse
events
decreased
neutrophil
count
anemia.
Adjudicated
drug-related
interstitial
lung
disease/pneumonitis
8
(9.3%).
These
findings
support
continued
exploration
HER2-positive
mCRC.
CA A Cancer Journal for Clinicians,
Journal Year:
2022,
Volume and Issue:
72(6), P. 524 - 541
Published: Oct. 3, 2022
Abstract
This
article
is
the
American
Cancer
Society’s
update
on
female
breast
cancer
statistics
in
United
States,
including
population‐based
data
incidence,
mortality,
survival,
and
mammography
screening.
Breast
incidence
rates
have
risen
most
of
past
four
decades;
during
recent
years
(2010–2019),
rate
increased
by
0.5%
annually,
largely
driven
localized‐stage
hormone
receptor‐positive
disease.
In
contrast,
mortality
declined
steadily
since
their
peak
1989,
albeit
at
a
slower
pace
(1.3%
annually
from
2011
to
2020)
than
previous
decade
(1.9%
2002
2011).
total,
death
dropped
43%
1989–2020,
translating
460,000
fewer
deaths
that
time.
The
similarly
for
women
all
racial/ethnic
groups
except
Indians/Alaska
Natives,
among
whom
were
stable.
However,
despite
lower
Black
versus
White
(127.8
vs.
133.7
per
100,000),
racial
disparity
remained
unwavering,
with
40%
higher
overall
(27.6
19.7
100,000
2016–2020)
two‐fold
adult
younger
50
(12.1
6.5
100,000).
lowest
5‐year
relative
survival
any
group
every
molecular
subtype
stage
disease
(except
I),
largest
Black–White
gaps
absolute
terms
receptor‐positive/human
epidermal
growth
factor
receptor
2‐negative
(88%
96%),
receptor‐negative/human
2‐positive
(78%
86%),
III
(64%
77%).
Progress
against
could
be
accelerated
mitigating
disparities
through
access
high‐quality
screening
treatment
via
nationwide
Medicaid
expansion
partnerships
between
community
stakeholders,
advocacy
organizations,
health
systems.
New England Journal of Medicine,
Journal Year:
2022,
Volume and Issue:
387(1), P. 9 - 20
Published: June 5, 2022
Among
breast
cancers
without
human
epidermal
growth
factor
receptor
2
(HER2)
amplification,
overexpression,
or
both,
a
large
proportion
express
low
levels
of
HER2
that
may
be
targetable.
Currently
available
HER2-directed
therapies
have
been
ineffective
in
patients
with
these
"HER2-low"
cancers.
Nature Medicine,
Journal Year:
2022,
Volume and Issue:
28(9), P. 1840 - 1847
Published: Aug. 8, 2022
Abstract
Trastuzumab
deruxtecan
is
an
antibody–drug
conjugate
with
high
extracranial
activity
in
human
epidermal
growth
factor
receptor
2
(HER2)-positive
metastatic
breast
cancer.
We
conducted
the
prospective,
open-label,
single-arm,
phase
TUXEDO-1
trial.
enrolled
patients
aged
≥18
years
HER2-positive
cancer
and
newly
diagnosed
untreated
brain
metastases
or
progressing
after
previous
local
therapy,
exposure
to
trastuzumab
pertuzumab
no
indication
for
immediate
therapy.
Patients
received
intravenously
at
standard
dose
of
5.4
mg
per
kg
bodyweight
once
every
3
weeks.
The
primary
endpoint
was
intracranial
response
rate
measured
according
assessment
neuro-oncology
criteria.
A
Simon
two-stage
design
used
compare
a
null
hypothesis
<26%
against
alternative
61%.
Fifteen
were
intention-to-treat
population
who
least
one
study
drug.
Two
(13.3%)
had
complete
response,
nine
(60%)
partial
three
(20%)
stable
disease
as
best
overall
73.3%
(95%
confidential
interval
48.1–89.1%),
thus
meeting
predefined
outcome.
No
new
safety
signals
observed
global
quality-of-life
cognitive
functioning
maintained
over
treatment
duration.
In
trial
(NCT04752059,
EudraCT
2020-000981-41),
showed
active
from
should
be
considered
option
this
setting.
International Journal of Molecular Sciences,
Journal Year:
2022,
Volume and Issue:
23(12), P. 6806 - 6806
Published: June 18, 2022
Breast
cancer
is
the
most
common
malignancy
in
women
worldwide.
Metastasis
leading
cause
of
high
mortality
cancers.
Although
predicting
early
stage
breast
before
metastasis
can
increase
survival
rate,
often
discovered
or
diagnosed
after
has
occurred.
In
general,
a
poor
prognosis
because
it
starts
as
local
disease
and
spread
to
lymph
nodes
distant
organs,
contributing
significant
impediment
treatment.
Metastatic
cells
acquire
aggressive
characteristics
from
tumor
microenvironment
(TME)
through
several
mechanisms
including
epithelial–mesenchymal
transition
(EMT)
epigenetic
regulation.
Therefore,
understanding
nature
mechanism
facilitate
development
targeted
therapeutics
focused
on
metastasis.
This
review
discusses
current
therapies
improve
diagnosis
patients
with
metastatic
cancer.
BMJ,
Journal Year:
2023,
Volume and Issue:
unknown, P. e071674 - e071674
Published: May 30, 2023
Triple
negative
breast
cancer
(TNBC)
continues
to
be
the
subtype
of
with
highest
rates
recurrence
and
mortality.
The
lack
expression
targetable
proteins
such
as
estrogen
receptor
absence
HER2
amplification
have
made
relying
on
cytotoxic
chemotherapy
necessary
for
decades.
In
operable
setting,
efforts
improve
outcomes
focused
escalation
systemic
therapy
a
shift
toward
preoperative
delivery
followed
by
response
adapted
approach
postoperative
therapy.
An
improved
understanding
tumor
biology
has
resulted
in
identification
subsets
patients
specific
molecular
features,
leading
testing
approval
multiple
new
targeted
therapies
this
disease.
Furthermore,
advances
drug
development
led
antibody-drug
conjugates
that
are
redefining
classification
schemes
cancer.
This
review
focuses
modern
management
TNBC,
particular
focus
recent
updates
treatment
disease,
an
overview
most
promising
therapeutic
landscape
metastatic
It
discusses
practical
challenges
unanswered
questions
resulting
from
neoadjuvant
immunotherapy
shares
clinic
topics
which
evidence
is
lacking.
addition,
it
provides
glimpse
into
future,
highlighting
opportunities
biomarker
based
right-sizing
therapy,
refining
evaluation
after
surgery,
early
diagnosis
detection
relapse,
areas
needed
research
TNBC.
