Frontiers in Immunology,
Год журнала:
2024,
Номер
15
Опубликована: Дек. 23, 2024
Background
Transarterial
therapy
(TAT),
bevacizumab
(Bev),
and
immune
checkpoint
inhibitors
(ICIs)
have
individually
exhibited
efficacy
in
treating
advanced-stage
hepatocellular
carcinoma
(HCC).
This
study
aimed
to
assess
the
safety
of
combination
these
three
treatments
as
a
neoadjuvant
modality
patients
with
locally
advanced
HCC.
Methods
The
primary
endpoint
is
overall
survival
(OS).
second
progression
free
(PFS),
objective
response
rate
(ORR),
pathological
safety.
Results
A
total
54
received
standard
systemic
comprising
Bev
combined
ICIs
(Bev-ICIs
group),
113
direct
surgery
(Surgery
273
TAT
plus
ICIs,
among
which
79
(28.9%)
underwent
surgical
resection
after
successful
tumor
downstaging
(Neo-surgery
group)
while
remaining
194
(71.1%)
maintenance
therapies
(Neo-maintenance
group).
Neoadjuvant
following
demonstrated
prolonged
OS
contrast
surgery,
median
time
not
reached
Neo-surgery
group
30.6
(95%
CI:
26.4-34.7)
months
Surgery
(hazard
ratio
(HR)=0.29,
P=0.0058).
PFS
groups
stood
at
19.2
16.1-22.2)
6.3
CI:4.7-8)
months,
respectively
(HR=0.25,
P<0.0001).
In
failed
receiving
therapy,
was
22.8
22.3-23.1)
whereas
that
for
care
population
19.7
15.9-24)
month
(HR=0.53,
P=0.023).
Neo-maintenance
Bev-ICIs
11.2
10.4-11.9)
6.4
4.4-8.5)
(HR=0.60,
P=0.024).
ORR
disease
control
(DCR)
across
all
TAT-Bev-ICIs
were
38.8%
89.4%,
respectively.
Additionally,
complete
(pCR)
major
(MPR)
22.8%
48.1%
group.
As
safety,
did
increase
perioperative
complications
when
compared
similar
incidences
severity
AEs
therapy.
Conclusion
triple
regimen
emerged
promising
therapeutic
strategy
(HCC)
intervention.
EClinicalMedicine,
Год журнала:
2023,
Номер
67, С. 102367 - 102367
Опубликована: Дек. 12, 2023
BackgroundThe
synergistic
effect
of
locoregional
therapy
in
combination
with
systemic
as
a
conversion
for
unresectable
hepatocellular
carcinoma
(uHCC)
is
unclear.
The
purpose
this
study
was
to
evaluate
the
efficacy
and
safety
transcatheter
arterial
chemoembolisation
(TACE)
combined
lenvatinib
camrelizumab
(TACE
+
LEN
CAM)
uHCC.MethodsThis
single-arm,
multicentre,
prospective
conducted
at
nine
hospitals
China.
Patients
(aged
18–75
years)
diagnosed
uHCC,
an
Eastern
Cooperative
Oncology
Group
performance
score
(ECOG-PS)
0–1
Child-Pugh
class
A
received
(200
mg,
every
3
weeks)
(bodyweight
≥60
kg:
12
mg/day;
<60
8
mg/day)
after
TACE
treatment.
Surgery
performed
tumour
assessed
meeting
criteria
resection.
who
did
not
meet
surgery
continued
receive
triple
until
disease
progression
or
intolerable
toxicity.
Primary
endpoints
were
objective
response
rate
(ORR)
according
modified
Response
Evaluation
Criteria
Solid
Tumours
(mRECIST)
safety.
Secondary
included
surgical
rate,
radical
(R0)
resection
control
(DCR).
This
registered
Chinese
Clinical
Trial
Registry
(ChiCTR2100050410).FindingsBetween
Oct
25,
2021,
July
20,
2022,
55
patients
enrolled.
As
data
cutoff
on
June
1,
2023,
median
follow-up
13.3
months
(IQR
10.6–15.9
months).
best
complete
(CR)
9
(16.4%)
patients,
partial
(PR)
33
(60.0%)
stable
(SD)
5
(9.1%)
progressive
(PD)
7
(12.7%)
patients.
ORR
76.4%
(42/55,
95%
CI,
65.2–87.6%),
DCR
85.5%
(47/55,
76.2–94.8%)
per
mRECIST.
Twenty-four
(43.6%)
suffered
from
grade
3–4
treatment-related
adverse
events
(TRAEs).
No
TRAEs
occurred.
total
30
(30/55,
54.5%)
converted
resectable
HCC
29
(29/55,
52.7%)
underwent
R0
96.6%
(28/29).
major
pathologic
(MPR)
(pCR)
rates
population
65.5%
(19/29)
20.7%
(6/29),
respectively.
Only
one
patient
developed
Clavien-Dindo
IIIa
complication
(abdominal
infection).
IIIb-V
complications
OS
PFS
reached.InterpretationThe
promising
active
uHCC
manageable
Moreover,
has
good
efficiency
feasible
safe.
To
elucidate
whether
accepting
treatment
can
achieve
better
survival
benefits
than
those
only,
well-designed
randomised
controlled
trials
are
needed.FundingThis
funded
by
Natural
Science
Foundation
Fujian
Province,
China
(2022J01691)
Youth
Province
Health
Technology
Project,
(2022QNA035).
Journal of Gastroenterology and Hepatology,
Год журнала:
2024,
Номер
39(4), С. 746 - 753
Опубликована: Янв. 19, 2024
Abstract
Background
and
Aim
The
study
aims
to
investigate
the
efficacy
safety
of
hepatic
arterial
infusion
chemotherapy
(HAIC)
combined
with
lenvatinib
immune
checkpoint
inhibitors
(ICIs)
versus
ICIs
for
hepatocellular
carcinoma
(HCC)
transarterial
chemoembolization
(TACE)
refractoriness.
Methods
Patients
intermediate
or
advanced
TACE‐refractory
HCC
who
received
without
HAIC
between
2020
2022
were
retrospectively
reviewed.
tumor
response,
overall
survival
(OS),
progression‐free
(PFS),
treatment‐related
adverse
events
(TRAEs)
evaluated
compared
two
groups.
Factors
affecting
OS
PFS
identified
univariate
multivariate
Cox
regression
analyses.
Results
A
total
121
patients
enrolled,
58
assigned
HAIC‐Len‐ICI
group
63
Len‐ICI
group.
higher
objective
response
rate
disease
control
found
in
than
(48.30%
vs
23.80%,
P
=
0.005;
87.90%
69.80%,
0.02,
respectively).
median
was
24.0
months
13.0
(
0.001).
7.2
<
Multivariable
analyses
suggested
that
presence
cirrhosis,
Child–Pugh
B
stage,
therapy
option
prognostic
factors
PFS.
incidences
any
grade
3/4
TRAEs
both
comparable
Conclusions
yielded
better
OS,
PFS,
ORR,
DCR
lenvatinib‐ICI
refractory
TACE,
manageable
events.
International Journal of Surgery,
Год журнала:
2024,
Номер
110(10), С. 6647 - 6657
Опубликована: Июль 12, 2024
Background:
The
high
recurrent
rate
after
liver
transplantation
(LT)
remains
a
clinical
challenge,
especially
for
those
exceeding
the
Milan
criteria
(MC)
and
with
RETREAT
scores.
Therefore,
authors
aim
to
investigate
whether
neoadjuvant
systemic
therapy
allows
safely
administered
effectively
reduces
post-LT
recurrence
patients.
Methods:
In
this
prospective,
randomized,
open-label,
pilot
study,
patients
HCC
MC
were
randomly
assigned
PLENTY
or
control
group
before
LT.
primary
endpoint
of
study
was
recurrence-free
survival
Results:
Twenty-two
enrolled
assigned:
11
group.
30-month
tumor-specific
RFS
37.5%
in
12.5%
12-month
LT
significantly
improved
(87.5%)
compared
(37.5%)
(
P
=0·0022).
objective
response
30
60%
when
determined
by
RECIST
1.1
mRECIST,
respectively.
Six
(60%)
had
significant
tumor
necrosis,
including
three
(30%)
who
complete
necrosis
at
histopathology.
No
acute
allograft
rejection
occurred
Control
Conclusion:
Neoadjuvant
pembrolizumab
plus
lenvatinib
appears
be
safe
feasible,
associated
better
MC.
Despite
limitations
small
sample
size,
is
first
RCT
evaluate
PD-1
blockade
combined
tyrosine
kinase
inhibitors
recipients,
results
will
inform
future
research.
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".
Journal of Hematology & Oncology,
Год журнала:
2024,
Номер
17(1)
Опубликована: Дек. 21, 2024
Lenvatinib
is
a
multi-target
tyrosine
kinase
inhibitor
widely
used
in
the
treatment
of
hepatocellular
carcinoma
(HCC).
Its
primary
mechanism
action
involves
inhibiting
signal
pathways
such
as
vascular
endothelial
growth
factor
receptors
(VEGFR)
and
fibroblast
(FGFR),
thereby
reducing
tumor
cell
proliferation
angiogenesis
affecting
tumor's
immune
microenvironment.
In
liver
cancer,
although
lenvatinib
monotherapy
has
shown
good
clinical
effect,
problem
drug
resistance
becoming
more
serious.
This
may
be
caused
by
variety
factors,
including
genetic
mutations,
signaling
pathway
remodeling,
changes
order
to
overcome
resistance,
combination
other
therapeutic
strategies
gradually
become
research
hotspot,
it
worth
noting
that
checkpoint
inhibitors
(ICIs)
application
prospect.
not
only
enhances
anti-tumor
response
but
also
helps
improve
efficacy.
However,
therapy
faces
challenges
regarding
safety
tolerability.
Therefore,
studying
mechanisms
identifying
relevant
biomarkers
particularly
important,
aids
early
diagnosis
personalized
treatment.
article
reviews
treating
efficacy
its
with
inhibitors,
causes
exploration
biomarkers,
novel
for
lenvatinib.
We
hope
provide
insights
into
use
scientific
settings,
offering
new
cancer.
Cancers,
Год журнала:
2023,
Номер
15(24), С. 5878 - 5878
Опубликована: Дек. 17, 2023
Triple
combination
conversion
therapy,
involving
transcatheter
arterial
chemoembolization
(TACE)
or
hepatic
infusion
chemotherapy
(HAIC)
combined
with
tyrosine
kinase
inhibitors
(TKIs)
and
immune
checkpoint
(ICIs),
has
shown
an
encouraging
objective
response
rate
(ORR)
successful
surgery
in
initially
unresectable
hepatocellular
carcinoma
(HCC).
However,
the
safety
long-term
survival
outcomes
of
subsequent
liver
resection
after
still
remain
to
be
validated.
From
February
2019
2023,
726
patients
were
enrolled
this
retrospective
study
(75
received
hepatectomy
therapy
[CLR
group],
651
underwent
pure
[LR
group]).
Propensity
score
matching
(PSM)
was
used
balance
preoperative
baseline
characteristics.
After
PSM,
68
CLR
group
124
LR
analyzed,
all
variables
well-balanced.
Compared
group,
experienced
longer
Pringle
maneuver
time,
operation
hospital
stays.
In
addition,
had
significantly
higher
incidence
rates
intra-abdominal
bleeding,
biliary
leakage,
post-hepatectomy
failure
(PHLF),
Clavien-Dindo
grade
IIIa
complications
than
group.
There
no
significant
statistical
differences
overall
(OS)
(hazard
ratio
[HR]
0.724;
95%
confidence
interval
[CI]
0.356-1.474;
p
=
0.374)
recurrence-free
(RFS)
(HR
1.249;
CI
0.807-1.934;
between
two
groups.
Liver
following
triple
HCC
may
achieve
favorable
manageable
profiles;
presenting
as
a
promising
treatment
option
for
HCC.
BioScience Trends,
Год журнала:
2024,
Номер
18(1), С. 42 - 48
Опубликована: Фев. 7, 2024
Therapies
for
patients
with
unresectable
hepatocellular
carcinoma
(uHCC)
are
currently
popular.
Current
first-line
standard-of-care
treatments
uHCC
systematic
therapies.
However,
that
combine
locoregional
therapy
systemic
widely
accepted
in
China
and
have
demonstrated
high
rates
of
tumor
response
conversion
to
resection
manageable
toxicity.
A
literature
review
was
performed
by
searching
published
PubMed
Web
Science
up
December
2023
relevant
articles
on
the
use
triple
(transarterial
chemoembolization
combined
lenvatinib
anti–PD-1
antibodies)
uHCC.
This
concentrates
efficacy
safety
Chinese
characteristics
describes
outcome
surgery,
degree
pathological
necrosis,
effect
prediction.
article
will
contribute
a
comprehensive
understanding
role
