ADJUVANT STUDY GEICAM/2011-03_S1007 (RxPONDER) AND

10º SIMPOSIO INTERNACIONAL
GEICAM. CÓRDOBA,
25-27CÓRDOBA,
MARZO 2015
10º SIMPOSIO INTERNACIONAL
GEICAM.
25-27 MARZO 2015
ADJUVANT ADJUVANT
STUDY GEICAM/2011-03_S1007
(RxPONDER)
AND ADVANCED
BREAST CANCER
(ABC)
STUDY
STUDY GEICAM/2011-03_S1007
(RxPONDER)
AND ADVANCED
BREAST
CANCER
(ABC) STUDY
TRIO-020 (GEICAM/2012-01),
ACTIVELY RECRUITING
PATIENTS IN
GEICAM IN GEICAM
TRIO-020 (GEICAM/2012-01),
ACTIVELY RECRUITING
PATIENTS
4, Álvarez I.5, Lluch
1,2Ruiz-Borrego
6, Martínez
7, Martínez
10, Alonso
11, Ruiz
12, De Toro
Alba E.1, Ruiz-Borrego
, Gil M.3, Ramos-Vázquez
A. 6, Martínez
N.7A.
, Martínez
E.8, N.
Chacón
JI.9, Ponce
J.10, Alonso
JL.11,J.Ruiz
I.12, DeJL.
Toro
S.13, I.
Carrasco
E.14
Martín
L.14, E.14, M
Alba E.M.
M.2, Gil M.3, M.
Ramos-Vázquez
M.4, Álvarez
I.5, Lluch
E.8, Chacón
JI.9, Ponce
S., 13
, Carrasco
14, 14
15 14
A..14, Carrasco
A.A..
Campo
R.14 and
A.R.
Del Monte C.14, Otero
Del Monte
C.14, Otero
, Carrasco
A.14,Antón
Campo
and Antón A.15
2Hospital Universitario
3ICO Hospitalet, Hospital
4Centro Oncológico de
1 Hospital Virgen
Hospital Clínico Universitario
la Victoria (Spain)
Virgen del
Rocío (Spain);
i Reynals
(Spain);
GaliciaOncológico
(Spain); 5Hospital
de Donostia
(Spain); 6de
Hospital
Clínicode
Universitario
Virgen ;de
la Victoria (Spain) ; 2Hospital
Universitario
Virgen
del Rocío (Spain); 3ICODuran
Hospitalet,
Hospital
Duran
i Reynals (Spain); 4Centro
de Galicia
(Spain); 5Hospital
Donostia (Spain
8Hospital Provincial de
9Hospital Virgen de la9Salud (Spain); 10Hospital General Universitario
Hospital
Universitario
Ramón yUniversitario
Cajal (Spain);
Castellón
(Spain); de
de Alicante
(Spain); 11de
Hospital
Virgen
de 11Hospita
Clínico Universitario de
Valencia
(Spain); 7de
Clínico
Universitario
Valencia
(Spain); 7Hospital
Ramón
y Cajal (Spain); 8Hospital
Provincial
Castellón (Spain); Hospital Virgen de la Salud (Spain); 10Hospital General
Universitario
Alicante
(Spain);
13Hospital de Jerez (Spain);
14GEICAM, Madrid (Spain);
15Hospital Universitario
12Hospital
la Arrixaca (Spain); 12Hospital
Sant
Joan de
Reus (Spain);
Miguel Servet
(Spain)Miguel Servet (Spain)
la Arrixaca
(Spain);
Sant Joan
de Reus (Spain); 13Hospital
de Jerez (Spain); 14GEICAM,
Madrid (Spain); 15Hospital
Universitario
1
GEICAM/2011-03_S1007
(RxPONDER):(RxPONDER):
A Phase III, Randomized
Trial of
Standard
Endocrine
Therapy
+/- Chemotherapy
in Patients in P
GEICAM/2011-03_S1007
A Phase III, clinical
Randomized
clinical
TrialAdjuvant
of Standard
Adjuvant
Endocrine
Therapy +/- Chemotherapy
with 1-3 Positive
Hormone
Receptor
Positive
and HER2Negative
Breast
Cancer
(ClinicalTrials.gov
Identifier: NCT01272037)
withNodes,
1-3 Positive
Nodes,
Hormone
Receptor
Positive
and HER2Negative
Breast
Cancer (ClinicalTrials.gov
Identifier: NCT01272037)
Background
Background
Study Design and
Treatment
Study
Design and Treatment
 Prospective randomized
trialsrandomized
indicate that
patients
withthathormone
 Prospective
trials
indicate
patients with hormone
receptor (HR)-positive
primary
breast cancer
benefit
from(BC)
the benefit from the
receptor
(HR)-positive
primary(BC)
breast
cancer
addition of chemotherapy
to adjuvant (CT)
endocrine
treatment
(1).
addition of(CT)
chemotherapy
to adjuvant
endocrine
treatment (1).
However, retrospective
analyses
of prospective
clinical
trials indicate
that trials indicate that
However,
retrospective
analyses
of prospective
clinical
some patients may
not patients
benefit from
with well-patients with wellsome
may CT,
not specifically,
benefit frompatients
CT, specifically,
differentiated tumors,
with hightumors,
expression
of HR,
or with of
lowHR,
or or with low or
differentiated
with high
expression
intermediate Recurrence
ScoreRecurrence
(RS) as defined
theasOncotype
DXthe Oncotype DX
intermediate
Score by
(RS)
defined by
assay (2-5).
assay (2-5).
 Multi-gene tumor
assays have
provided
useful prognostic
 Multi-gene
tumor
assays clinically
have provided
clinically useful prognostic
information for patients
with node-negative
BC.node-negative
The 21-geneBC.
RS The
has 21-gene RS has
information
for patients with
been shown to be,
bothshown
prognostic
patients
with estrogen
receptor
been
to be,for
both
prognostic
for patients
with estrogen receptor
(ER)-positive disease
treated with
tamoxifen
alone,
well as predictive
(ER)-positive
disease
treated
with as
tamoxifen
alone, as well as predictive
for the benefit of adding
for theCT.
benefit of adding CT.
 In retrospective analyses,
patientsanalyses,
with highpatients
RS appeared
to RS
benefit
In retrospective
with high
appeared to benefit
greatly from the addition
of standard
CT tooftamoxifen,
whereas
those whereas those
greatly from
the addition
standard CT
to tamoxifen,
with low RS did not
This
now helps
to guide
patients
Current Status Current Status
with(4,5).
low RS
didassay
not (4,5).
This assay
now
helps and
to guide patients and
physicians decision
making, decision
for determining
for the
patients
physicians
making,the
for treatment
determining
treatment for patients
Recruitment Curve
in Spain Curve in Spain
Recruitment
Number
of
patients
to
be
included
:
4,000
(800
planned
in
Spain).
Number
of
patients
to
be
included
:
4,000
(800
planned
in
Spain).
with node-negative,
HR-positive
disease.
Furthermore,
retrospective
and retrospective and
with
node-negative,
HR-positive
disease.
Furthermore,
900
900
patients:
3,326 (631
in Spain).
prospective studies
have indicated
RS result
Current included
patients:
3,326 (631 in Spain).
prospective
studies that
havetheindicated
thatchanges
the RS the
result Current
changesincluded
the
800
adjuvant recommendation
17 to 26% of the
cases,
in current
800
adjuvant in
recommendation
in 17
to 26%
of the clinical
cases, in current clinical
Centre Name
Patients Screened
PatientsScreened
Included
Centre Name
Patients
Patients Included
practice (6).
practice (6).
700
700
H. Virgen del Rocio
H. Virgen del Rocio120
ICO (BCN)
100
ICO (BCN)
Objectives
Objectives
H. Virgen de la VictoriaH. Virgen de la Victoria
85
C. Oncológico de Galicia
65
C. Oncológico de Galicia
H. Donostia
76
H. Donostia
Primary objective:
Primary objective:
H. Clínico de Valencia H. Clínico de Valencia
60
 To determine the
of chemotherapy
with node
positivewith node positive
 effect
To determine
the effect in
of patients
chemotherapy
in patients
H. Ramón y Cajal
H. Ramón y Cajal 71
H. Provincial
de Castellón
53
breast cancer who
do not
havewho
highdoRecurrence
Scores
(RS) by Scores (RS)
H. Provincial de Castellón
breast
cancer
not have high
Recurrence
by
H. Virgen de la Salud H. Virgen de la Salud38
Oncotype DX® Oncotype DX®
IVO
66
IVO
ICO (Girona)
ICO (Girona) 33
Secondary objectives:
Secondary objectives:
H. Miguel Servet
H. Miguel Servet 54
 To compare Overall
andSurvival
distant recurrence-free
survival
 To Survival
compare(OS)
Overall
(OS) and distant
recurrence-free survival
H. Lozano Blesa
H. Lozano Blesa 42
H. Santa
27
(DRFS) by type (DRFS)
of treatment
and ofto treatment
determineand
the tointeraction
H. Santa Creu i Sant Pau
by type
determineofthe interaction
of Creu i Sant Pau
Onkologikoa
26
Onkologikoa
treatment and RS.treatment and RS.
H. Clinic i Provincial H. Clinic i Provincial34
 To compare toxicity
arms.
 To between
compareboth
toxicity
between both arms.
H. San Pedro de Alcántara
14
H. San Pedro de Alcántara
 To Perform other
assays
or tests
particular
the (in
PAM50
risk of
 To
Perform
other (in
assays
or tests
particular
the PAM50 riskH.of
Gregorio Marañón H. Gregorio Marañón13
relapse score in arelapse
direct and
real
comparison)
that measure
the that measure the
score
in time
a direct
and real time
comparison)
H. Infanta Cristina
H. Infanta Cristina 14
potential benefit potential
of chemotherapy
to compare and
themto compare
with
Germans Trias i Pujol
20
benefit ofand
chemotherapy
them H.with
H. Germans Trias i Pujol
H. Gral. Albacete
H. Gral. Albacete 12
Oncotype DX.
Oncotype DX.
80
120
66
100
60
85
48
65
46
76
45
60
40
71
33
53
33
38
32
66
29
33
27
54
18
42
15
27
14
26
13
34
11
14
8
13
7
14
5
20
1
12
80
600
66
600
60
PLANNED
500
500
48
PATIENTS
46
ENROLLED
400
400
PATIENTS
45
300
300
40
33
200
200
33
100
32
100
29
0
0
27
oct.-12 sep.-13 ago.-14
jul.-15
jun.-16
oct.-12
sep.-13
ago.-14 jul.-15
jun.-16
18
15
References
References
14
1,13
Lancet 2005;365:1687-717.
15894097
1, LancetPMID:
2005;365:1687-717.
PMID: 15894097
2.11
Lancet 2004; 364:858-68.
PMID:
15351193
2. Lancet
2004;
364:858-68. PMID: 15351193
3.8JAMA 2006; 295:1658-67.
PMID:
3. JAMA
2006;16609087
295:1658-67. PMID: 16609087
4.7N Engl J Med. 2004;4.
351:2817-26.
PMID:
N Engl J Med.
2004;15591335
351:2817-26. PMID: 1559
5.5J Clin Oncol 2006; 24:3726-34.
PMID:
16720680
5. J Clin Oncol
2006;
24:3726-34. PMID: 1672068
6.1J Oncol Practice 2007;
6. J3:182-6
Oncol Practice 2007; 3:182-6
TRIO-020 (GEICAM/2012-01):
A randomizedAopen-label
Phase
II studyPhase
of letrozole
afatinib (BIBW2992)
letrozole
alone
in the first-line
TRIO-020 (GEICAM/2012-01):
randomized
open-label
II studyplus
of letrozole
plus afatinibversus
(BIBW2992)
versus
letrozole
alone in the firsttreatment of advanced
HER2- postmenopausal
breast cancer,breast
with low
ER expression
Identifier: NCT02115048)
treatment ER+,
of advanced
ER+, HER2- postmenopausal
cancer,
with low ER(ClinicalTrials.gov
expression (ClinicalTrials.gov
Identifier: NCT02115048)
Background
Study Design and
Treatment
Study
Design and Treatment
Background
 Around 2/3 of human
estrogen
receptors
ER (1).receptors ER (1).
Around BC
2/3 express
of human
BC express
estrogen
Endocrine therapyEndocrine
with aromatase
represents
the treatment
therapyinhibitors
with aromatase
inhibitors
represents the treatment
of choice for postmenopausal
with hormone
receptor-positive
of choice for women
postmenopausal
women
with hormone receptor-positive
(HR+) advanced (HR+)
BC (ABC),
particularly
for those
with slowly
advanced
BC (ABC),
particularly
for those with slowly
progressive disease
and limited
tumor-related
symptoms
(2).
progressive
disease
and limited
tumor-related
symptoms (2).
 Previous biomarker
research
identified
a correlation
 Previous
biomarker
research
identified between
a correlation between
quantitative HR measurements
the responseand
to the
lapatinib
and to lapatinib and
quantitative HRand
measurements
response
paclitaxel in a cohort
of women
HER2
negative
ABC
(3). negative ABC (3).
paclitaxel
in awith
cohort
of women
with
HER2
 Other studies have
suggested
relationship
between
peptide growth
 Other
studiesahave
suggested
a relationship
between peptide growth
factor signaling and
HR signaling
status (4).and HR status (4).
factor
Arm A
Postmenopausal Postmenopausal
women with ER+, women with ER+,
(low ER
(low ER
expression),
expression),
R
HER2 negative HER2 negative
ABC, with no priorABC, with
Arm no
B prior
systemic therapy systemic therapy
for advanced
for advanced
disease
disease
Oral Letrozole 2.5 mg/daily
Oral Letrozole 2.5 mg/daily
Arm A
Progressive
Disease
R
or
Other
Arm B
Withdrawal
Oral Letrozole 2.5 mg/daily
Oral Letrozole 2.5Criteria
mg/dailymet
Oral Afatinib 30 mg/daily
Oral Afatinib 30 mg/daily
 The addition oflapatinib
to letrozole
in postmenopausal
with
The addition
of lapatinib
to letrozole in women
postmenopausal
women with
HR+ (low ER expression)
HER2-negative,
have shown
HR+ (low ER
expression) ABC,
HER2-negative,
ABC, have shown
significant improvement
in Progression-Free
Survival (PFS) (5).Survival (PFS) (5).
significant
improvement in Progression-Free
Current Status Current Status
 The proposed 
study
afatinibstudy
is designed
to test
hypothesis
Status in Spain: Status in Spain:
Thewith
proposed
with afatinib
is the
designed
to test the hypothesis
 4 participant
 4 participant
that low ER expression
as determined
by determined
semi-quantitative
that low ER
expression as
by semi-quantitative
countries: USA,
countries:
2 USA,
2
immunohistochemistry
(IHC) is a biomarker
forisHER-dependence
in
immunohistochemistry
(IHC)
a biomarker for HER-dependence
in
REGISTERED
Romania, Bosnia
Romania, Bosnia
women with HER2women
negative
BC.
with
HER2 negative BC.
RANDOMIZED
and Spain.
and Spain.
Objectives
Objectives
Primary objective:
To assess
PFS in both
arms.PFS in both arms.
Primary
objective:
To assess
Secondary objectives:
Secondary objectives:
 150 patients are
required to be
included: 50 in
Spain.
 To assess the Overall
safety the
profile.
 To assess
Overall safety profile.
1
 150 patients are
required to be
included:0 50 in
Spain.
1
0
Accrual curve:
References
Accrual curve:
40
40
Overall ENROLMENT - PLANNED
Overall ENROLMENT - PLANNED
35
REGISTERED
35
Cumulative (N pts)
Cumulative (N pts)
RANDOMIZED
30
30 - ACTUAL
Overall SCREENING
Overall SCREENING - ACTUAL
Cumulative (N pts)
Cumulative (N pts)
25
25
20
15
10
 11 patients have  11 patients have
been already
been already
recruited; 2 in
recruited; 2 in
Spain.
Spain.
 To assess Overall
Rate Response Rate
 To survival
assess (OS),
OverallObjective
survival Response
(OS), Objective
(ORR) and Time to(ORR)
Tumorand
Progression
(TTP).Progression (TTP).
Time to Tumor
F
O
Progressive
L
Disease
L or
OOther
Withdrawal
W
Criteria met
U
P
Overall ENROLMENT - ACTUAL
Overall ENROLMENT - ACTUAL
20
Cumulative (N pts)
Cumulative (N pts)
15 - ACTUAL
Spain ENROLMENT
Spain ENROLMENT - ACTUAL
Cumulative (N pts)
Cumulative (N pts)
10
5
5
0
0
11
2
References
1. Harvey JM, Clark GM,
CK,Clark
et al.GM,
J Clin
Oncol, CK,
1999:
1. Osborne
Harvey JM,
Osborne
et 17:1474-81.
al. J Clin Oncol, 1999: 17:1474-81.
Exploratory objectives
(Optional):
To
examine
the
molecular
Exploratory objectives (Optional): To examine the 2.molecular
Hurvitz SA, Pietras RJ.
Cancer,SA,
2008:
113:2385-97
2. Hurvitz
Pietras
RJ. Cancer, 2008: 113:2385-97
profiles of tumorprofiles
tissue of
submitted
to identify
factorsto that
may factors that
tumor tissue
submitted
identify
may
3. Finn RS, Press MF, Dering
et al.
J Clin
3. FinnJ,RS,
Press
MF,Oncol,
Dering2009:
J, et 27:3908-15.
al. J Clin Oncol, 2009: 27:3908-15.
influence on biological
and on
clinical
responses
to studyresponses
treatments.
influence
biological
and clinical
to study treatments.
4. Arpino G, Weiss H, Lee
AV, et G,
al. Weiss
J Natl Cancer
Inst,et2005:
97:1254-61.
4. Arpino
H, Lee AV,
al. J Natl
Cancer Inst, 2005: 97:1254-61.
5. Finn et al. Clin Can Res,
5. Finn2014.
et al. Clin Can Res, 2014.
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