Nivolumab plus ipilimumab versus lenvatinib or sorafenib as first-line treatment for unresectable hepatocellular carcinoma (CheckMate 9DW): an open-label, randomised, phase 3 trial
The Lancet,
Год журнала:
2025,
Номер
unknown
Опубликована: Май 1, 2025
Patients
with
unresectable
hepatocellular
carcinoma
have
a
poor
prognosis,
and
treatments
long-term
benefits
are
needed.
We
report
results
from
the
preplanned
interim
analysis
of
CheckMate
9DW
trial
assessing
nivolumab
plus
ipilimumab
versus
lenvatinib
or
sorafenib
for
in
first-line
setting.
This
open-label,
randomised,
phase
3
enrolled
patients
aged
18
years
older
without
previous
systemic
therapy
at
163
hospitals
cancer
centres
across
25
countries
Asia,
Australia,
Europe,
North
America,
South
America.
had
least
one
measurable
untreated
lesion
per
Response
Evaluation
Criteria
Solid
Tumours
(RECIST)
version
1.1,
Child-Pugh
score
5
6,
an
Eastern
Cooperative
Oncology
Group
performance
status
0
1.
were
randomly
assigned
(1:1)
via
interactive
response
technology
system
to
receive
(1
mg/kg)
(3
intravenously
every
weeks
up
four
doses,
followed
by
480
mg
4
investigator's
choice
either
oral
(8
12
daily
depending
on
bodyweight)
(400
twice
daily).
Randomisation
was
stratified
aetiology;
presence
macrovascular
invasion,
extrahepatic
spread,
both;
baseline
alpha-fetoprotein
concentration.
The
primary
endpoint
overall
survival,
which
assessed
all
patients;
safety
exploratory
who
received
dose
study
medication.
is
registered
ClinicalTrials.gov,
NCT04039607
(ongoing).
Between
Jan
2020,
Nov
8,
2021,
668
(n=335)
(n=333).
Early
crossing
survival
Kaplan-Meier
curves
reflected
higher
number
deaths
during
first
6
months
after
randomisation
(hazard
ratio
1·65
[95%
CI
1·12-2·43])
but
sustained
separation
thereafter
favour
(0·61
[0·48-0·77]).
After
median
follow-up
35·2
(IQR
31·1-39·9),
significantly
improved
(median
23·7
18·8-29·4]
vs
20·6
[17·5-22·5];
hazard
0·79
[0·65-0·96];
two-sided
log-rank
p=0·018);
respective
rates
49%
(95%
44-55)
39%
(34-45)
24
38%
(32-43)
24%
(19-30)
36
months.
Overall,
137
(41%)
332
receiving
138
(42%)
325
grade
3-4
treatment-related
adverse
events.
attributed
treatment
three
sorafenib.
Nivolumab
showed
significant
benefit
manageable
previously
carcinoma.
These
support
as
this
Bristol
Myers
Squibb.
Язык: Английский
Clinical Manifestations and Risk Factors of Liver Injury Induced by PD-1 Inhibitors in Patients with Malignancies: A Case-Control Study
Therapeutics and Clinical Risk Management,
Год журнала:
2025,
Номер
Volume 21, С. 309 - 320
Опубликована: Март 1, 2025
Background:
Hepatic
injury
induced
by
immune
checkpoint
inhibitors
(ICPIs)
is
an
inevitable
challenge
in
the
era
of
innovative
anti-tumor
therapies.
However,
studies
on
immune-related
liver
are
relatively
insufficient,
and
associated
risk
factors
still
lacking.
The
purpose
this
study
was
to
explore
incidence
clinical
manifestations
immunotherapy-related
injury.
Methods:
A
retrospective
case-control
conducted
involving
patients
treated
with
PD-1
at
Weifang
People's
Hospital,
a
tertiary
general
hospital
China,
from
January
1,
2021
July
31,
2024.
Univariate
multivariate
logistic
regression
analyses
were
employed
identify
potential
factors.
Then,
predictive
value
these
evaluated
using
receiver
operating
characteristic
(ROC)
curve
analysis.
Results:
In
total,
300
included.
Among
patients,
52
experienced
mean
time
initiation
immunotherapy
onset
28.4
days,
range
2
219
days.
71.15%
developed
within
first
30
82.69%
presented
mild
cases
(grade
1),
13.46%
moderate
2),
3.84%
severe
(grades
3–
4).
overall
inhibitors-related
0.34%.
Specifically,
nivolumab
exhibited
highest
2.86%,
followed
sintilimab
0.41%.
Both
toripalimab
camrelizumab
0.34%,
while
tislelizumab
had
lowest
0.28%.
Multivariate
analysis
showed
that
GGT
AST
independent
for
ROC
revealed
baseline
ALT≥
19.5
U/L,
AST≥
GGT≥
28.5
U/L
increased
developing
Conclusion:
therapy,
close
monitoring
function
recommended,
especially
during
inhibitors.
Keywords:
inhibitors,
adverse
events,
injury,
incidence,
Язык: Английский