Cancer Discovery,
Journal Year:
2018,
Volume and Issue:
8(11), P. 1390 - 1403
Published: Sept. 11, 2018
CDK4/6
inhibition
with
endocrine
therapy
is
now
a
standard
of
care
for
advanced
estrogen
receptor-positive
breast
cancer.
Mechanisms
inhibitor
resistance
have
been
described
preclinically,
limited
evidence
from
clinical
samples.
We
conducted
paired
baseline
and
end-of-treatment
circulating
tumor
DNA
sequencing
195
patients
in
the
PALOMA-3
randomized
phase
III
trial
palbociclib
plus
fulvestrant
versus
placebo
fulvestrant.
show
that
clonal
evolution
occurs
frequently
during
treatment,
reflecting
substantial
subclonal
complexity
cancer
has
progressed
after
prior
therapy.
npj Breast Cancer,
Journal Year:
2019,
Volume and Issue:
5(1)
Published: Jan. 11, 2019
Abstract
At
the
MONARCH
3
interim
analysis,
abemaciclib
plus
a
nonsteroidal
aromatase
inhibitor
(AI)
significantly
improved
progression-free
survival
(PFS)
and
objective
response
rate
(ORR)
with
tolerable
safety
profile
as
initial
treatment
for
hormone
receptor-positive
(HR+),
human
epidermal
growth
factor
receptor
2-negative
(HER2−)
advanced
breast
cancer
(ABC).
is
randomized,
phase
III,
double-blind
study
of
abemaciclib/placebo
(150
mg
twice
daily,
continuous)
AI
(1
anastrozole
or
2.5
letrozole,
daily).
A
total
493
postmenopausal
women
HR+,
HER2−
ABC
no
prior
systemic
therapy
in
this
setting
were
enrolled.
The
primary
endpoint
was
investigator-assessed
PFS
(final
analysis
after
240
events);
other
endpoints
included
evaluations.
Here
we
analyze
final
data
update
secondary
endpoints.
arm
had
longer
median
than
placebo
(28.18
versus
14.76
months;
hazard
ratio
[95%
confidence
interval],
0.540
[0.418–0.698];
p
=
.000002).
ORR
61.0%
45.5%
(measurable
disease,
.003).
duration
(27.39
months)
compared
to
(17.46
months).
consistent
previous
reports.
most
frequent
grade
≥
adverse
events
arms
neutropenia
(23.9%
1.2%),
diarrhea
(9.5%
leukopenia
(8.6%
0.6%).
Abemaciclib
an
effective
acceptable
ABC.
Cancer Discovery,
Journal Year:
2018,
Volume and Issue:
8(11), P. 1390 - 1403
Published: Sept. 11, 2018
CDK4/6
inhibition
with
endocrine
therapy
is
now
a
standard
of
care
for
advanced
estrogen
receptor-positive
breast
cancer.
Mechanisms
inhibitor
resistance
have
been
described
preclinically,
limited
evidence
from
clinical
samples.
We
conducted
paired
baseline
and
end-of-treatment
circulating
tumor
DNA
sequencing
195
patients
in
the
PALOMA-3
randomized
phase
III
trial
palbociclib
plus
fulvestrant
versus
placebo
fulvestrant.
show
that
clonal
evolution
occurs
frequently
during
treatment,
reflecting
substantial
subclonal
complexity
cancer
has
progressed
after
prior
therapy.
