European Urology,
Год журнала:
2024,
Номер
unknown
Опубликована: Окт. 1, 2024
Innovations
have
improved
outcomes
in
advanced
prostate
cancer
(PC).
Nonetheless,
we
continue
to
lack
high-level
evidence
on
a
variety
of
topics
that
greatly
impact
daily
practice.
The
2024
Advanced
Prostate
Cancer
Consensus
Conference
(APCCC)
surveyed
experts
key
questions
clinical
management
order
supplement
evidence-based
guidelines.
Here
present
voting
results
for
from
APCCC
2024.
Drugs,
Год журнала:
2024,
Номер
84(9), С. 1093 - 1109
Опубликована: Июль 26, 2024
Despite
recent
advances
in
the
treatment
of
metastatic
prostate
cancer,
progression
to
a
castration-resistant
state
remains
inevitable
for
most
and
prognosis
is
limited.
Genetic
testing
homologous
recombination
repair
pathway
alterations
recommended
all
patients
with
advanced
cancer
given
that
mutation
present
up
25%
cases.
Poly(ADP-ribose)
polymerase
(PARPis)
are
now
approved
use
who
have
progressed
on
an
androgen
receptor
inhibitor
(ARPI)
harbour
germline
or
somatic
mutation.
Preclinical
data
support
synergistic
effect
ARPI
PARPi,
various
ARPI-PARPi
combinations
therefore
been
explored
phase
III
clinical
trials.
heterogeneous
findings,
clear
hierarchy
benefit
evident,
harbouring
BRCA
deriving
greatest
magnitude
benefit,
followed
by
any
The
repair-proficient
cohort
less
clear,
questions
remain
about
whether
combination
therapy
should
be
offered
without
With
ARPIs
considered
standard-of-care
hormone-sensitive
currently
being
earlier
paradigm.
purpose
this
review
discuss
rationale
behind
therapy,
summarise
results
key
trials,
considerations
future
perspectives.
JCO Precision Oncology,
Год журнала:
2024,
Номер
8
Опубликована: Авг. 1, 2024
PURPOSE
Outcomes
data
for
DNA-damaging
therapeutics
men
with
prostate
cancer
(PC)
and
non-
BRCA1/2
homologous
recombination
repair
(HRR)
mutations
are
limited.
We
evaluated
outcomes
by
HRR
alteration
in
PC
treated
poly(ADP-ribose)polymerase
inhibitors
(PARPi)
and/or
platinum
chemotherapy.
METHODS
Retrospective
from
the
PROMISE
consortium
were
used.
Clinical
differences
assessed
between
patients
BRCA1/
2
(cohort
A)
those
without
direct
BRCA
complex
interaction
B:
ATM,
CDK12,
CHEK1,
CHEK2,
FANCL).
also
explored
C:
RAD51B/C/D,
RAD54L2,
BARD1,
GEN1,
PALB2,
FANCA,
BRIP1).
RESULTS
One
hundred
forty-six
received
PARPi
A:
94,
cohort
45,
7)
104
chemotherapy
48,
44,
10).
PSA50
response
rate
to
was
higher
A
(61%)
than
B
(5%),
P
<
.001.
Median
clinical/radiographic
progression-free
survival
(crPFS)
significantly
longer
15.9
versus
8.7
months,
=
.005.
therapy
(62%)
(32%),
.024,
although
crPFS
not
different.
40%
32%,
respectively,
C.
In
multivariable
analysis,
had
improved
overall
compared
but
CONCLUSION
Patients
BRCA1/2-mutated
interaction.
CA A Cancer Journal for Clinicians,
Год журнала:
2025,
Номер
unknown
Опубликована: Янв. 10, 2025
Abstract
Poly(adenosine
diphosphate
ribose)
polymerase
(PARP)
inhibitors,
such
as
olaparib,
talazoparib,
rucaparib,
and
niraparib,
comprise
a
therapeutic
class
that
targets
PARP
proteins
involved
in
DNA
repair.
Cancer
cells
with
homologous
recombination
repair
defects,
particularly
BRCA
alterations,
display
enhanced
sensitivity
to
these
agents
because
of
synthetic
lethality
induced
by
inhibitors.
These
have
significantly
improved
survival
outcomes
across
various
malignancies,
initially
gaining
regulatory
approval
ovarian
cancer
subsequently
breast,
pancreatic,
prostate
cancers
different
indications.
This
review
offers
comprehensive
clinical
overview
inhibitor
approvals,
emphasizing
their
efficacy
based
on
landmark
phase
3
trials.
