Clinical Cancer Research,
Journal Year:
2023,
Volume and Issue:
29(17), P. 3340 - 3351
Published: June 28, 2023
Plasma
circulating
tumor
DNA
(ctDNA)
analysis
is
used
for
genotyping
advanced
non-small
cell
lung
cancer
(NSCLC);
monitoring
dynamic
ctDNA
changes
may
be
to
predict
outcomes.This
was
a
retrospective,
exploratory
of
two
phase
III
trials
[AURA3
(NCT02151981),
FLAURA
(NCT02296125)].
All
patients
had
EGFR
mutation-positive
(EGFRm;
ex19del
or
L858R)
NSCLC;
AURA3
also
included
T790M-positive
NSCLC.
Osimertinib
(FLAURA,
AURA3),
comparator
EGFR-tyrosine
kinase
inhibitor
(EGFR-TKI;
gefitinib/erlotinib;
FLAURA),
platinum-based
doublet
chemotherapy
(AURA3)
given.
EGFRm
analyzed
at
baseline
and
Weeks
3/6
by
droplet
digital
PCR.
Outcomes
were
assessed
detectable/non-detectable
plasma
clearance
(non-detection)
3/6.In
(n
=
291),
non-detectable
versus
detectable
longer
median
progression-free
survival
[mPFS;
HR,
0.48;
95%
confidence
interval
(CI),
0.33-0.68;
P
<
0.0001].
In
with
Week
3
non-clearance
184),
respectively,
mPFS
(months;
CI)
10.9
(8.3-12.6)
5.7
(4.1-9.7)
osimertinib
6.2
(4.0-9.7)
4.2
(4.0-5.1)
platinum-pemetrexed.
499),
(HR,
0.54;
CI,
0.41-0.70;
0.0001).
For
334),
19.8
(15.1
not
calculable)
11.3
(9.5-16.5)
10.8
(9.7-11.1)
7.0
(5.6-8.3)
EGFR-TKI.
Similar
outcomes
observed
6
clearance/non-clearance.Plasma
as
early
weeks
on-treatment
has
the
potential
in
Annals of Oncology,
Journal Year:
2023,
Volume and Issue:
35(1), P. 77 - 90
Published: Oct. 23, 2023
Amivantamab
plus
carboplatin-pemetrexed
(chemotherapy)
with
and
without
lazertinib
demonstrated
antitumor
activity
in
patients
refractory
epidermal
growth
factor
receptor
(EGFR)-mutated
advanced
non-small-cell
lung
cancer
(NSCLC)
phase
I
studies.
These
combinations
were
evaluated
a
global
III
trial.
Journal of Clinical Oncology,
Journal Year:
2023,
Volume and Issue:
41(35), P. 5363 - 5375
Published: Sept. 10, 2023
Patritumab
deruxtecan,
or
HER3-DXd,
is
an
antibody-drug
conjugate
consisting
of
a
fully
human
monoclonal
antibody
to
epidermal
growth
factor
receptor
3
(HER3)
attached
topoisomerase
I
inhibitor
payload
via
stable
tetrapeptide-based
cleavable
linker.
We
assessed
the
efficacy
and
safety
HER3-DXd
in
patients
with
(
Annals of Oncology,
Journal Year:
2024,
Volume and Issue:
35(7), P. 588 - 606
Published: May 27, 2024
Advancements
in
the
field
of
precision
medicine
have
prompted
European
Society
for
Medical
Oncology
(ESMO)
Precision
Medicine
Working
Group
to
update
recommendations
use
tumour
next-generation
sequencing
(NGS)
patients
with
advanced
cancers
routine
practice.
New England Journal of Medicine,
Journal Year:
2024,
Volume and Issue:
391(16), P. 1486 - 1498
Published: June 26, 2024
BackgroundAmivantamab
plus
lazertinib
(amivantamab–lazertinib)
has
shown
clinically
meaningful
and
durable
antitumor
activity
in
patients
with
previously
untreated
or
osimertinib-pretreated
EGFR
(epidermal
growth
factor
receptor)–mutated
advanced
non–small-cell
lung
cancer
(NSCLC).MethodsIn
a
phase
3,
international,
randomized
trial,
we
assigned,
2:2:1
ratio,
EGFR-mutated
(exon
19
deletion
L858R),
locally
metastatic
NSCLC
to
receive
amivantamab–lazertinib
(in
an
open-label
fashion),
osimertinib
blinded
fashion,
assess
the
contribution
of
treatment
components).
The
primary
end
point
was
progression-free
survival
group
as
compared
group,
assessed
by
independent
central
review.ResultsOverall,
1074
underwent
randomization
(429
amivantamab–lazertinib,
429
osimertinib,
216
lazertinib).
median
significantly
longer
than
(23.7
vs.
16.6
months;
hazard
ratio
for
disease
progression
death,
0.70;
95%
confidence
interval
[CI],
0.58
0.85;
P<0.001).
An
objective
response
observed
86%
(95%
CI,
83
89)
85%
those
81
88)
group;
among
confirmed
(336
314
group),
duration
25.8
months
20.1
could
not
be
estimated)
16.8
14.8
18.5),
respectively.
In
planned
interim
overall
analysis
death
0.80
0.61
1.05).
Predominant
adverse
events
were
EGFR-related
toxic
effects.
incidence
discontinuation
all
agents
due
treatment-related
10%
3%
osimertinib.ConclusionsAmivantamab–lazertinib
showed
superior
efficacy
first-line
NSCLC.
(Funded
Janssen
Research
Development;
MARIPOSA
ClinicalTrials.gov
number,
NCT04487080.)
Journal of Clinical Oncology,
Journal Year:
2024,
Volume and Issue:
42(11), P. 1252 - 1264
Published: Jan. 22, 2024
PURPOSE
The
phase
III
CheckMate
722
trial
(ClinicalTrials.gov
identifier:
NCT02864251
)
evaluated
nivolumab
plus
chemotherapy
versus
in
patients
with
epidermal
growth
factor
receptor
(
EGFR)–mutated
metastatic
non–small-cell
lung
cancer
(NSCLC)
after
disease
progression
on
EGFR
tyrosine
kinase
inhibitors
(TKIs).
METHODS
Patients
first-
or
second-generation
TKI
therapy
(without
T790M
mutation)
osimertinib
(with/without
were
randomly
assigned
1:1
to
(360
mg
once
every
3
weeks)
platinum-doublet
(once
alone
for
four
cycles.
Primary
end
point
was
progression-free
survival
(PFS).
Secondary
points
included
9-
and
12-month
PFS
rates,
overall
(OS),
objective
response
rate
(ORR),
duration
of
(DOR).
RESULTS
Overall,
294
assigned.
At
final
analysis
(median
follow-up,
38.1
months),
not
significantly
improved
(median,
5.6
v
5.4
months;
hazard
ratio
[HR],
0.75
[95%
CI,
0.56
1.00];
P
=
.0528),
rates
25.9%
19.8%,
21.2%
15.9%,
respectively.
Post
hoc
subgroup
analyses
showed
a
trend
favoring
tumors
harboring
sensitizing
mutations
(HR,
0.72
0.54
0.97]),
one
line
previous
(0.72
both
(0.64
0.47
0.88]).
Median
OS
19.4
months
15.9
chemotherapy,
while
ORR
31.3%
26.7%,
median
DOR
6.7
months,
Grade
3/4
treatment-related
adverse
events
occurred
44.7%
29.4%
treated
alone,
CONCLUSION
Nivolumab
did
improve
EGFR-mutated
NSCLC
previously
TKIs.
No
new
safety
signals
identified.
