ESMO Gastrointestinal Oncology,
Год журнала:
2023,
Номер
1, С. 27 - 39
Опубликована: Окт. 1, 2023
Immune
checkpoint
inhibition
(ICI)
has
revolutionized
cancer
therapy,
including
treatment
of
hepatocellular
carcinoma
(HCC)
which
comprises
80%-90%
all
liver
cancers,
the
third
most
common
cause
cancer-related
death
worldwide.
The
main
targeted
pathways
are
cytotoxic
T-lymphocyte-associated
protein-4
(CTLA-4)
and
programmed
cell
protein
1
(PD-1)/programmed
death-ligand
(PD-L1)
checkpoints.
Blockade
CTLA-4
with
monoclonal
antibodies
leads
to
an
activation
increase
in
effector
T
cells
that
can
interact
tumor
cells.
Additionally,
inhibitory
regulatory
reduced,
leading
immunosupportive
microenvironment.
PD-1/PD-L1
reduces
immunosuppression
directly
within
tissue
reactivates
immune
response
Recently,
HIMALAYA
trial
shown
dual
ICI
CTLA-4-blocking
antibody
tremelimumab
PD-L1-directed
durvalumab
(STRIDE
regimen)
is
superior
sorafenib
regarding
efficacy
safety
advanced
HCC
unprecedented
long-term
survival
data
for
these
patients.
combination
(atezolizumab)
anti-vascular
endothelial
growth
factor
(bevacizumab)
significantly
improved
outcomes
compared
been
clinical
use
since
2020.
Looking
at
outcome
measures
ICI,
radiologically
assessed
endpoints
such
as
progression-free
objective
rate
only
modestly
correlate
overall
survival.
modified
RECIST
criteria
seem
better
identify
responders
conventional
imaging
evaluation
criteria.
So
far,
predictive
biomarkers
a
robust
understanding
impact
underlying
diseases
largely
lacking.
An
accurate
stratification
patients
based
on
etiology
potential
further
improve
HCC.
Frontiers in Immunology,
Год журнала:
2024,
Номер
15
Опубликована: Авг. 5, 2024
Hepatocellular
carcinoma
(HCC)
is
one
of
the
most
common
cancers
and
third
leading
cause
death
worldwide.
surgery,
transarterial
chemoembolization
(TACE),
systemic
therapy,
local
ablation
radiotherapy,
targeted
drug
therapy
with
agents
such
as
sorafenib.
However,
tumor
microenvironment
liver
cancer
has
a
strong
immunosuppressive
effect.
Therefore,
new
treatments
for
are
still
necessary.
Immune
checkpoint
molecules,
programmed
death-1
(PD-1),
death-ligand
1
(PD-L1),
cytotoxic
T
lymphocyte
antigen-4
(CTLA-4),
along
high
levels
cytokines,
induce
cell
inhibition
key
mechanisms
immune
escape
in
HCC.
Recently,
immunotherapy
based
on
inhibitors
(ICIs)
monotherapy
or
combination
tyrosine
kinase
inhibitors,
anti-angiogenesis
drugs,
chemotherapy
agents,
topical
therapies
offered
great
promise
treatment
cancer.
In
this
review,
we
discuss
latest
advances
ICIs
combined
drugs
(targeted-immune
combination)
other
targeted-immune
regimens
patients
advanced
HCC
(aHCC)
unresectable
(uHCC),
provide
an
outlook
future
prospects.
The
literature
reviewed
spans
last
five
years
includes
studies
identified
using
keywords
"hepatocellular
carcinoma,"
"immune
inhibitors,"
"targeted
therapy,"
"combination
"immunotherapy".
Current Oncology,
Год журнала:
2023,
Номер
30(6), С. 5863 - 5875
Опубликована: Июнь 18, 2023
The
liver
maintains
a
balance
between
immune
tolerance
and
activation
in
its
role
as
filtration
system.
Chronic
inflammation
disrupts
this
microenvironment,
thereby
allowing
for
the
rise
progression
of
cancer.
Hepatocellular
carcinoma
(HCC)
is
tumor
generally
diagnosed
setting
chronic
disease.
When
early,
primary
treatment
surgical
resection,
transplantation,
or
directed
therapies.
Unfortunately,
patients
with
HCC
often
present
at
an
advanced
stage
poor
function,
limiting
options.
To
further
complicate
matters,
most
systemic
therapies
are
relatively
limited
ineffective
among
Recently,
IMbrave150
trial
demonstrated
that
combination
atezolizumab
bevacizumab
was
associated
better
survival
compared
to
sorafenib
HCC.
As
such,
now
recommended
first-line
therapy
these
patients.
Tumor
cells
work
create
immunotolerant
environment
by
preventing
stimulatory
immunoreceptors
upregulating
expression
proteins
bind
inhibitory
immunoreceptors.
ICIs
block
interactions
bolster
anti-tumor
function
We
herein
provide
overview
use
International Journal of Molecular Sciences,
Год журнала:
2023,
Номер
24(14), С. 11799 - 11799
Опубликована: Июль 22, 2023
A
combination
of
atezolizumab
with
bevacizumab
(AB)
is
the
first
regimen
that
has
shown
superiority
compared
to
sorafenib
and
now
being
used
as
systemic
treatment
choice
for
hepatocellular
carcinoma
(HCC)
patients
Barcelona
Liver
Cancer
Clinic
stage
C.
However,
a
considerable
number
do
not
achieve
survival
or
significant
responses,
indicating
need
identify
predictive
biomarkers
initial
on-treatment
decisions
in
HCC
receiving
AB.
In
this
manuscript,
we
summarized
current
data
from
both
experimental
clinical
studies.
This
review
will
be
beneficial
clinicians
researchers
practice
well
those
designing
experimental,
translational,
Liver Cancer,
Год журнала:
2024,
Номер
unknown, С. 1 - 11
Опубликована: Май 22, 2024
<b><i>Introduction:</i></b>
The
combination
of
atezolizumab/bevacizumab
has
emerged
as
an
effective
first-line
treatment
for
advanced
hepatocellular
carcinoma
(HCC).
However,
this
therapy
is
potentially
associated
with
bleeding
complications,
warranting
a
comprehensive
analysis
their
incidence
and
severity.
This
meta-analysis
aims
to
synthesize
available
evidence
from
clinical
trials
observational
studies
quantify
the
prevalence
following
administration.
<b><i>Methods:</i></b>
focused
on
HCC
using
atezolizumab/bevacizumab,
particularly
examining
complications.
It
determined
post-administration
compared
risk
ratio
tyrosine
kinase
inhibitors
(sorafenib
or
lenvatinib).
Risk
factors
complications
were
also
evaluated.
<b><i>Results:</i></b>
From
28
involving
3,895
patients,
pooled
side
effects
was
8.42%
(95%
CI:
5.72–11.54).
Grade
III
IV
occurred
in
4.42%
2.64–6.10)
grade
V
observed
2.06%
0.56–4.22).
Gastrointestinal
bleeding,
predominantly
variceal,
most
common,
5.48%
3.98–7.17).
Subgroup
indicated
variability
rates
based
study
design
geographical
location.
Atezolizumab/bevacizumab
exhibited
2.11
times
higher
1.21–3.66).
Meta-regression
identified
high
body
mass
index
(BMI)
proportion
albumin-bilirubin
(ALBI)
3
significant
<b><i>Conclusion:</i></b>
carries
heightened
gastrointestinal
exceeding
that
inhibitors.
High
BMI
ALBI
are
key
predictors
emphasizing
need
cautious
patient
selection
monitoring.
Seminars in Liver Disease,
Год журнала:
2024,
Номер
44(02), С. 159 - 179
Опубликована: Май 1, 2024
Primary
liver
cancer,
represented
mainly
by
hepatocellular
carcinoma
(HCC)
and
intrahepatic
cholangiocarcinoma
(CCA),
is
one
of
the
most
common
deadliest
tumors
worldwide.
While
surgical
resection
or
transplantation
are
best
option
in
early
disease
stages,
these
often
present
advanced
stages
systemic
treatment
required
to
improve
survival
time.
The
emergence
immune
checkpoint
inhibitor
(ICI)
therapy
has
had
a
positive
impact
especially
on
cancers,
thereby
establishing
immunotherapy
as
part
first-line
HCC
CCA.
Nevertheless,
low
response
rates
reflect
usually
cold
immunosuppressed
tumor
microenvironment
primary
cancer.
In
this
review,
we
aim
summarize
mechanisms
resistance
leading
escape
with
special
focus
composition
both
CCA,
also
reflecting
recent
important
developments
ICI
combination
therapy.
Furthermore,
discuss
how
ICIs
established
cancer
treatments
(e.g.
multikinase
inhibitors
chemotherapy)
well
more
complex
combinations
state-of-the-art
therapeutic
concepts
may
reshape
microenvironment,
higher
long-lasting
antitumor
immunity
for
patients.
Journal of Gastroenterology,
Год журнала:
2024,
Номер
unknown
Опубликована: Сен. 18, 2024
Abstract
Background
Although
atezolizumab
plus
bevacizumab
(Atezo/Bev)
therapy
has
been
used
as
the
preferred
first-line
treatment
for
advanced
hepatocellular
carcinoma
(HCC),
up
to
26%
of
patients
do
not
achieve
disease
control,
suggesting
alternative
treatments
might
be
more
beneficial
such
patients.
We
investigated
key
predictors
refractoriness
Atezo/Bev
therapy,
particularly
in
setting.
Methods
retrospectively
analyzed
302
with
HCC
who
received
between
October
2020
and
September
2022
across
nine
hospitals
Japan.
Refractoriness
was
defined
best
overall
response
(BOR)
progressive
or
stable
a
progression-free
survival
(PFS)
<
180
days
(RECIST
v1.1).
Clinical
benefit
BOR
partial/complete
PFS
≥
days.
Baseline
characteristics
potential
predictors,
identified
through
literature
review,
were
compared
these
groups.
Stratifications
(OS),
also
assessed.
Results
observed
126
(41.7%)
patients,
while
154
(51.0%)
achieved
clinical
benefit.
Due
significant
association
line
refractory
rate,
subsequent
analysis
focused
on
cohort
(
n
=
214;
72
[33.6%]
showed
refractoriness).
Among
13
CRP
AFP
immunotherapy
(CRAFITY)
score
had
predictive
performance,
rates
24.6%,
44.6%,
57.9%
CRAFITY-0,
1,
2
respectively
p
0.001).
OS
well-stratified
by
this
scoring
system.
Conclusions
Approximately
one-third
therapy.
The
CRAFITY
demonstrated
superior
performance
predicting
refractoriness.
