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.
New England Journal of Medicine,
Journal Year:
2016,
Volume and Issue:
375(20), P. 1925 - 1936
Published: Nov. 16, 2016
A
phase
2
study
showed
that
progression-free
survival
was
longer
with
palbociclib
plus
letrozole
than
alone
in
the
initial
treatment
of
postmenopausal
women
estrogen-receptor
(ER)–positive,
human
epidermal
growth
factor
receptor
(HER2)–negative
advanced
breast
cancer.
We
performed
a
3
designed
to
confirm
and
expand
efficacy
safety
data
for
this
indication.
Journal of Clinical Oncology,
Journal Year:
2017,
Volume and Issue:
35(32), P. 3638 - 3646
Published: Oct. 2, 2017
Purpose
Abemaciclib,
a
cyclin-dependent
kinase
4
and
6
inhibitor,
demonstrated
efficacy
as
monotherapy
in
combination
with
fulvestrant
women
hormone
receptor
(HR)-positive,
human
epidermal
growth
factor
2
(HER2)-negative
advanced
breast
cancer
previously
treated
endocrine
therapy.
Methods
MONARCH
3
is
double-blind,
randomized
phase
III
study
of
abemaciclib
or
placebo
plus
nonsteroidal
aromatase
inhibitor
493
postmenopausal
HR-positive,
HER2-negative
who
had
no
prior
systemic
therapy
the
setting.
Patients
received
(150
mg
twice
daily
continuous
schedule)
either
1
anastrozole
2.5
letrozole,
daily.
The
primary
objective
was
investigator-assessed
progression-free
survival.
Secondary
objectives
included
response
evaluation
safety.
A
planned
interim
analysis
occurred
after
189
events.
Results
Median
survival
significantly
prolonged
arm
(hazard
ratio,
0.54;
95%
CI,
0.41
to
0.72;
P
=
.000021;
median:
not
reached
arm,
14.7
months
arm).
In
patients
measurable
disease,
rate
59%
44%
(
.004).
diarrhea
most
frequent
adverse
effect
(81.3%)
but
mainly
grade
(44.6%).
Comparing
placebo,
events
were
neutropenia
(21.1%
v
1.2%),
(9.5%
leukopenia
(7.6%
0.6%).
Conclusion
Abemaciclib
effective
initial
therapy,
improving
demonstrating
tolerable
safety
profile
cancer.
New England Journal of Medicine,
Journal Year:
2015,
Volume and Issue:
373(3), P. 209 - 219
Published: June 1, 2015
Growth
of
hormone-receptor-positive
breast
cancer
is
dependent
on
cyclin-dependent
kinases
4
and
6
(CDK4
CDK6),
which
promote
progression
from
the
G1
phase
to
S
cell
cycle.
We
assessed
efficacy
palbociclib
(an
inhibitor
CDK4
CDK6)
fulvestrant
in
advanced
cancer.This
3
study
involved
521
patients
with
hormone-receptor-positive,
human
epidermal
growth
factor
receptor
2-negative
that
had
relapsed
or
progressed
during
prior
endocrine
therapy.
randomly
assigned
a
2:1
ratio
receive
placebo
fulvestrant.
Premenopausal
perimenopausal
women
also
received
goserelin.
The
primary
end
point
was
investigator-assessed
progression-free
survival.
Secondary
points
included
overall
survival,
objective
response,
rate
clinical
benefit,
patient-reported
outcomes,
safety.
A
preplanned
interim
analysis
performed
by
an
independent
data
safety
monitoring
committee
after
195
events
disease
death
occurred.The
median
survival
9.2
months
(95%
confidence
interval
[CI],
7.5
not
estimable)
palbociclib-fulvestrant
3.8
CI,
3.5
5.5)
placebo-fulvestrant
(hazard
for
death,
0.42;
95%
0.32
0.56;
P<0.001).
most
common
grade
adverse
group
were
neutropenia
(62.0%,
vs.
0.6%
group),
leukopenia
(25.2%
0.6%),
anemia
(2.6%
1.7%),
thrombocytopenia
(2.3%
0%),
fatigue
(2.0%
1.2%).
Febrile
reported
palbociclib-treated
placebo-treated
patients.
discontinuation
due
2.6%
1.7%
placebo.Among
metastatic
who
therapy,
combined
resulted
longer
than
alone.
(Funded
Pfizer;
PALOMA3
ClinicalTrials.gov
number,
NCT01942135.).
Genes & Diseases,
Journal Year:
2018,
Volume and Issue:
5(2), P. 77 - 106
Published: May 12, 2018
As
the
most
commonly
occurring
cancer
in
women
worldwide,
breast
poses
a
formidable
public
health
challenge
on
global
scale.
Breast
consists
of
group
biologically
and
molecularly
heterogeneous
diseases
originated
from
breast.
While
risk
factors
associated
with
this
varies
respect
to
other
cancers,
genetic
predisposition,
notably
mutations
