Novedades en tratamiento con quimioterapia en Cáncer de Mama

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Novedades en tratamiento con quimioterapia en Cáncer de Mama
Novedades en tratamiento con
quimioterapia en Cáncer de Mama
Dr E Ciruelos
S Oncología Médica
Hospital 12 de Octubre, Madrid
Evolución de la quimioterapia
en cáncer de mama avanzado
Mid 20th
century
Early
chemotherapy
CMF (VP)
Late 20th
century
Anthracyclines
Vinorelbine
Late 20th
century
Taxanes
Capecitabine
Early 21st century
Biological
era
begins
Novel antitubulins
Advanced cytotoxics
CMF = cyclophosphamide + methotrexate + 5-flourouracil; VP = vincristine + prednisone
A quién tratar con QT?
Factores que determinan la elección del tratamiento
en el cáncer de mama avanzado
Características
de la enfermedad
Carga de enfermedad
Características de la
paciente
Terapia adyuvante previa
Respuesta a terapias
previas
Agresividad de la
enfermedad
Elección del
tratamiento
Preferencia de la paciente
(oral vs IV), toxicidades
Aspectos socioeconómicos
y psicológicos
(ej.: distancia desde la casa
y el hospital, costes)
Edad, PS, comorbilidades
Estatus de RH (ER y
PgR) y HER2
Disponibilidad
Coste del tratamiento
Intervalo libre de
enfermedad
Estado menopáusico: SI vs. NO
Guías y recomendaciones
ABC2 Guidelines, Ann Oncol 2014
ALGORITMO DE TRATAMIENTO
Paciente postmenopáusica* con cancer de mama avanzado
RH+ y HER2-
Continuar con
la terapia
hormonal
hasta
progresión
o toxicidad
inaceptable
Progresión
Sin beneficio clínico
luego de varios
regímenes
consecutivos de
terapia hormonal
O
Enfermedad
visceral sintomática
Sí
Quimioterapia
No
EECC con
una nueva
terapia
hormonal
Cáncer de mama TN: Subtipos intrínsecos
Prat A. The Oncologist 2013
Nuevas formulaciones:
Nuevos fármacos
Nuevas formulaciones:
Nuevos fármacos
Nab-Paclitaxel
QT clásica: Nuevas formulaciones
Cáncer de mama metastásico: Nanotecnología
Abraxane
nab-Paclitaxel
PFS,
months
300 mg/m2
q3w
Arm A
(n = 76)
76
67
9
Media
n
10.9
10.9
13.8
64
12
39
25
26
49
N
All patients
< 65 years
≥ 65 years
DM
Visceral
Nonvisceral
Lesion sites
<5
≥5
Premenopausal
Postmenopausal
a Based
100 mg/m2
qw 3/4
Arm B
(n = 76)
Docetaxel
150 mg/m2
qw 3/4
Arm C
(n = 74)
100 mg/m2
q3w
Arm D
(n = 74)
Overall
P
valuea
N
Median
N
Median
76
62
14
Media
n
7.5
7.5
9.2
74
64
10
14.6
14.1
18.9
74
55
19
7.8
7.6
8.5
.008
.012
.564
10.9
16.4
61
15
7.5
7.7
59
15
13.1
> 19.2
67
7
7.8
11.0
.022
.575
10.2
12.1
11.0
10.9
37
24
14
62
8.7
6.9
7.5
7.5
38
21
21
53
13.1
14.1
12.9
14.6
41
26
12
60
7.6
7.8
5.6
8.4
.417
.009
.137
.022
N
on log-rank test.
DM, dominant metastasis; PFS, progression-free survival; q3w, every 3 weeks; qw
3/4, first 3 of 4 weeks.
Gradishar W. et al. ECCO. 2011 [Abstract 5060].
12
GeparSepto: Phase III Neoadjuvant Trial of nab-P vs sb-P
Regimens in Early Breast Cancer
Final Study Design (after 400 patients)
HER, human epidermal growth factor receptor; HR, hormone receptor; nab-P, nab-paclitaxel; sb-P, solvent-based paclitaxel.
Untch M, Jackisch C, Schneeweiss A, et al. A randomized phase III trial comparing nanoparticle-based paclitaxel with solvent-based paclitaxel as part of
neoadjuvant chemotherapy for patients with early breast cancer GBG 69 – GeparSepto. Oral presented at: San Antonio Breast Cancer Symposium
December 9 -13 , 2014; San Antonio, Texas. [oral S2-07].
13
GeparSepto: Phase III Neoadjuvant Trial of nab-P vs sb-P
Regimens in Early Breast Cancer
Primary Endpoint (pCR: ypT0 ypN0)
nab-P, nab-paclitaxel; pCR, pathological complete response; sb-P, solvent-based paclitaxel.
Untch M, Jackisch C, Schneeweiss A, et al. A randomized phase III trial comparing nanoparticle-based paclitaxel with solvent-based paclitaxel as part of
neoadjuvant chemotherapy for patients with early breast cancer GBG 69 – GeparSepto. Oral presented at: San Antonio Breast Cancer Symposium
December 9 -13 , 2014; San Antonio, Texas. [oral S2-07].
14
GeparSepto: Phase III Neoadjuvant Trial of nab-P vs sb-P
Regimens in Early Breast Cancer
Secondary Endpoints: pCR Rates According to
Other Definitions
nab-P, nab-paclitaxel; pCR, pathological complete response; sb-P, solvent-based paclitaxel.
Untch M, Jackisch C, Schneeweiss A, et al. A randomized phase III trial comparing nanoparticle-based paclitaxel with solvent-based paclitaxel as part of
neoadjuvant chemotherapy for patients with early breast cancer GBG 69 – GeparSepto. Oral presented at: San Antonio Breast Cancer Symposium
December 9 -13 , 2014; San Antonio, Texas. [oral S2-07].
15
GeparSepto: Phase III Neoadjuvant Trial of nab-P vs sb-P
Regimens in Early Breast Cancer
pCR in Stratified Subgroups
Parameter
Subgroup
pCR, %
P Value
SPARC
SPARC−
SPARC+
28.8 vs 37.7
29.8 vs 48.3
0.003
0.074
Ki67
Ki67 ≤ 20%
Ki67 >20%
19.6 vs 26.1
33.1 vs 44.0
0.137
0.001
Biological
subtype
HER2−, HR+
HER2−, HR−
HER2+, HR+
HER2+, HR−
12.0 vs 16.0
25.7 vs 48.2
50.0 vs 56.4
66.7 vs 74.6
0.183
< 0.001
0.275
0.371
HER2
HER2−
HER2+
17.7 vs 27.0
54.1 vs 61.8
< 0.001
0.120
HR status
HR−
HR+
36.1 vs 56.1
25.6 vs 29.9
< 0.001
0.169
HER, human epidermal growth factor receptor; HR, hormone receptor; nab-P, nab-paclitaxel; pCR, pathological complete response; sb-P, solvent-based
paclitaxel; SPARC, secreted protein acidic and rich in cysteine.
Untch M, Jackisch C, Schneeweiss A, et al. A randomized phase III trial comparing nanoparticle-based paclitaxel with solvent-based paclitaxel as part of
neoadjuvant chemotherapy for patients with early breast cancer GBG 69 – GeparSepto. Oral presented at: San Antonio Breast Cancer Symposium
December 9 -13 , 2014; San Antonio, Texas. [oral S2-07].
Nuevas formulaciones:
Nuevos fármacos
Etirinotecan
Etirinotecan (NKTR 102)
•
•
•
•
•
Pegilado en polímero (prodroga inactiva)
Se libera en capilares de microvasculatura tumoral
Hidrólisis a droga activa
Inhibición de síntesis de DNA
No pico plasmático
Etirinotecan: Fase II en CMM
ORR, RECIST v 1.0
n/N (%)
Evaluable Patients
NKTR-102
145 mg/m2
q14 days
NKTR-102
145 mg/m2
q21 days
TOTAL
7/22 (32%)
5/21 (24%)
12/43 (28%)
Triple Negative
2/8 (25%)
5/10 (50%)
7/18 (39%)
Prior A/T/C
2/6 (33%)
3/10 (30%)
5/16 (31%)
Median PFS (m)
3.5
5.3
4.6
Median OS (m)
8.8
13.1
10.3
Prior A/T
Awada A, et al. IMPAKT 2012
Etirinotecan: Estudio BEACON
N=840
• CMM o localmente
recurrente
• 2-5 líneas previas QT
– ≥2 líneas en CMM
– Previo A, T y Cape
PI: J. Cortés
NKTR-102
145 mg/m2 /21d
R
1:1
Tratamiento a elección (TPC) *
Monoterapia (eribulina, ixabepilona,
vinorelbina, gemcitabina, taxanos)
Estratificación
• Area geográfica
• Eribulina previa
• Subtipo histológico
* Eribulina 40%, VNR 23%, gemcitabina 18%, taxano 15%, ixabepilona 4%
Etirinotecan: Estudio BEACON
• Median OS 12.4 vs 10.3 months (HR 0.87; p 0.08)
• Brain mets (67 pts): mOS 10 vs 4.8 m (HR 0.51; p<0.01)
• Liver mets (456 pts): mOS 10.9 vs 8.3 m (HR 0.73; p 0.002)
• Grade > 3 AEs: 48 vs 63%
Perez EA, ASCO June 2015
Antimicrotúbulos no taxanos
Eribulina
Eribulin’s novel mechanism of inhibiting microtubule
dynamics (Jordan et al., 2005)
Eribulin
Microtubule
Dynamics
1
Eribulin inhibits microtubule growth
Microtubule
Polymerization
3
Growing
microtubule
Eribulin causes globular tubulin
aggregates
Eribulin
MTOC
Microtubule
Depolymerization
Shortening
microtubule
2
Eribulin has no effect on
microtubule shortening
MT drawing created by M. Asada, TRL, Eisai; later adapted by B. Littlefield, ERI
Globular
tubulin aggregates
Phase II studies confirmed activity of eribulin in patients
with pre-treated MBC
201 Study1
(N=103):
Prior taxane &
anthracycline*
211 Study2
(N=299):
Prior taxane,
anthracycline,
& capecitabine*
Primary endpoint:
•
ORR with
independent review
• ORR: 11.5%
• Median DOR: 5.6 months
• Median PFS: 2.6 months
• 6-month PFS 25.9% (95% CI, 15.5, 36.3)
• Median OS: 9.0 months (range 0.5–27.2
months)
• 6-month survival 67.8% (95% CI, 58.0, 77.6)
• 1-year survival 45.7% (95% CI, 35.2, 56.2)
Secondary endpoints:
•
DOR, PFS, OS, AEs
• ORR: 9.3%
• Median DOR: 4.1 months
• Median PFS: 2.6 months
• 6-month PFS 15.6% (95% CI, 10.7, 20.5)
• Median OS: 10.4 months
• 6-month survival 72.3% (95% CI, 66.9, 77.6)
*MBC patients with progression of disease ≤6 months of last chemotherapy and, if present, pre-existing neuropathy ≤grade 2
AEs = adverse events; CI = confidence interval; DOR = duration of response; MBC = metastatic breast cancer; ORR = overall response rate; OS = overall survival;
PFS = progression-free survival
1. Vahdat L, Pruitt B et al. J Clin Oncol. 2009;27:2954–2961; 2. Cortes
J, Vahdat L et al. J Clin Oncol. 2010;28:3922–3928
Halaven has been evaluated in two of the largest,
Phase 3 randomised trials conducted in MBC1,2
EMBRACE study1
(N=762)
Study 3012
(N=1102)
La indicación en segunda línea en la que se administró el fármaco a los s pacientes en el
estudio 301 no está financiada por el sistema nacional de salud.
•2 prior regimens for advanced disease
•2 prior regimens for advanced disease
•Median of four prior chemotherapy
regimens
•HER2-negative 74%; TNBC 19%
•Comparator: single TPC
•Primary endpoint: OS
•Secondary endpoints: PFS, ORR, DOR
– 3 prior chemotherapy regimens
• 1 prior chemotherapy: 573 patients
– All prior anthracycline/taxane (25/46%
refractory)
•HER2-negative 68.5%; TNBC 26.0%
•Comparator: capecitabine
•Co-primary endpoints: OS and PFS
•Secondary endpoints: ORR, survival at 1,
2 and 3 years, QoL
DOR, duration of response; ORR, objective response rate; QoL, quality of life; TPC, treatment of physician’s choice.
In EMBRACE study, TPC was defined as any single-agent chemotherapy, hormonal therapy or targeted therapy approved for the treatment of
cancer, radiotherapy, or best supportive care. TPC was selected prior to randomisation to eliminate any bias. 1
1. Cortes J, et al. Lancet. 2011;377:914–923; 2. Kaufman PA, et al. J Clin Oncol. 20 Feb 2015 .
Halaven has been evaluated in two of the largest,
Phase 3 randomised trials conducted in MBC1,2
EMBRACE study1
(N=762)
Study 3012
(N=1102)
La indicación en segunda línea en la que se administró el fármaco a los s pacientes en el
estudio 301 no está financiada por el sistema nacional de salud.
•2 prior regimens for advanced disease
•2 prior regimens for advanced disease
•Median of four prior chemotherapy
regimens
•HER2-negative 74%; TNBC 19%
•Comparator: single TPC
•Primary endpoint: OS
•Secondary endpoints: PFS, ORR, DOR
– 3 prior chemotherapy regimens
• 1 prior chemotherapy: 573 patients
– All prior anthracycline/taxane (25/46%
refractory)
•HER2-negative 68.5%; TNBC 26.0%
•Comparator: capecitabine
•Co-primary endpoints: OS and PFS
•Secondary endpoints: ORR, survival at 1,
2 and 3 years, QoL
DOR, duration of response; ORR, objective response rate; QoL, quality of life; TPC, treatment of physician’s choice.
In EMBRACE study, TPC was defined as any single-agent chemotherapy, hormonal therapy or targeted therapy approved for the treatment of
cancer, radiotherapy, or best supportive care. TPC was selected prior to randomisation to eliminate any bias. 1
1. Cortes J, et al. Lancet. 2011;377:914–923; 2. Kaufman PA, et al. J Clin Oncol. 2015 [Epub ahead of print].
EMBRACE: Updated OS analysis
Median OS, months
Eribulin (n=508)
13.2
TPC (n=254)
10.5
HR
0.81
95% CI
0.67, 0.96
P value*
0.014
Analysis occurred at 589 events (deaths), representing 77% of the ITT population
*Nominal P value from stratified log-rank test
CI = confidence interval; HR = hazard ratio; ITT = intent-to-treat; OS = overall survival; TPC = treatment of physician’s choice
Cortes J, O’Shaughnessy J et al. Lancet. 2011;377:914–923;
Twelves C, Loesch D et al. San Antonio Breast Cancer Symposium. 2010;Poster P6-14-18
Halaven has been evaluated in two of the largest,
Phase 3 randomised trials conducted in MBC1,2
EMBRACE study1
(N=762)
Study 3012
(N=1102)
La indicación en segunda línea en la que se administró el fármaco a los s pacientes en el
estudio 301 no está financiada por el sistema nacional de salud.
•2 prior regimens for advanced disease
•2 prior regimens for advanced disease
•Median of four prior chemotherapy
regimens
•HER2-negative 74%; TNBC 19%
•Comparator: single TPC
•Primary endpoint: OS
•Secondary endpoints: PFS, ORR, DOR
– 3 prior chemotherapy regimens
• 1 prior chemotherapy: 573 patients
– All prior anthracycline/taxane (25/46%
refractory)
•HER2-negative 68.5%; TNBC 26.0%
•Comparator: capecitabine
•Co-primary endpoints: OS and PFS
•Secondary endpoints: ORR, survival at 1,
2 and 3 years, QoL
DOR, duration of response; ORR, objective response rate; QoL, quality of life; TPC, treatment of physician’s choice.
In EMBRACE study, TPC was defined as any single-agent chemotherapy, hormonal therapy or targeted therapy approved for the treatment of
cancer, radiotherapy, or best supportive care. TPC was selected prior to randomisation to eliminate any bias. 1
1. Cortes J, et al. Lancet. 2011;377:914–923; 2. Kaufman PA, et al. J Clin Oncol. 20 Feb 2015 .
Study 301
Study 301: A trend toward improved overall survival
with eribulin vs capecitabine (ITT population)
Median OS (co-primary endpoint) vs capecitabine showed a numerical difference in
favour of Halaven, but was not statistically significant
1.0
Median OS (months)
Proportion of survival
0.9
Eribulin (n=554)
15.9
Capecitabine (n=548)
14.5
0.7
HR
0.879
0.6
95% CI
0.770, 1.003
P value*
0.0560
0.8
0.5
There was no difference in PFS between the 2 treatment
arms
0.4
0.3
0.2
0.1
0.0
Number of subjects at risk
554 530 505 464 423 378 349 320 268 243 214 193 173 151 133 119 99
548 513 466 426 391 352 308 277 242 214 191 175 155 135 122 108 81
0
4
8
12
16
20
24
28
32
77
62
52
42
36
38
33
32
27
26
23
40
Time (months)
*Stratified log-rank test based on geographical region and HER2 status.
One-, 2-, and 3-year survival rates were 64.4% and 58.0% (P=0.04), 32.8% and 29.8% (P=0.32), and
17.8% and 14.5% (P=0.18) for eribulin and capecitabine, respectively.
Halaven Summary of Product Characteristics. www.ema.europa.eu; Kaufman PA, et al. J Clin Oncol. 2015 [Epub ahead of print].
22
17
44
15
13
13
12
48
9
10
7
2
52
Breast Cancer Res Treat. Sep 2014
DOI 10.1007/s10549-014-3144-y
CLINICAL TRIAL
Efficacy of eribulin in women with metastatic
breast cancer: a pooled analysis of two
phase 3 studies
Chris Twelves • Javier Cortes • Linda Vahdat •
Martin Olivo • Yi He • Peter A. Kaufman •
Ahmad Awada
Overall survival in the ITT population:
1.0
Median OS
(months)
0.9
Eribulin (n=1062)
15.2
Control (n=802)
12.8
0.7
HR
0.853
0.6
95% CI
0.768, 0.948
P value
0.0031
Proportion of survival
0.8
0.5
2.4 months
difference
0.4
0.3
0.2
0.1
0.0
Number of subjects at risk
1062
802
1021
750
957
672
870
604
785
545
690
486
623
414
554
370
462
324
385
275
327
242
276
216
227
181
189
151
158
134
130
113
105
83
0
2
4
6
8 10 12 14 16 18 20 22 24 26 28 30 32 34 36 38 40 42 44 46 48 50 52 54 56 58
Time (months)
Hazard ratio stratified by region, HER2 status, prior capecitabine use and study
Overall survival curves adjusted by study
305 study data is updated 77% event analysis
79
62
52
42
38
33
32
27
26
23
22
17
15
13
13
12
9
10
7
2
2
2
2
1
Data on file ERI-104
0
0
Overall survival in HER2 subgroups
Median OS
(months)
Event/N
Subgroup Eribulin
Overall
Control
HR (95% CI)
832/1062 662/802
P value Eribulin Control
0.853 (0.768, 0.948) 0.0031
15.2
12.8
HER2 status
Positive
139/169
110/123
0.815 (0.624, 1.063) 0.1345
13.5
12.2
Negative 581/748
467/572
0.841 (0.743, 0.952) 0.0062
15.2
12.3
Negative* 581/748
467/572
0.819 (0.722, 0.929) 0.0019
15.2
12.3
TNBC patients
Yes
201/243
162/185
0.741 (0.599, 0.917) 0.0056
12.9
8.2
No
543/707
441/543
0.862 (0.757, 0.981) 0.0243
15.7
13.7
0.4
0.6
Favours eribulin
*Additionally
stratified by triple-negative status
0.8
1.0
1.2
1.4
1.6
Favours control
1.8
Toxicidad
Estudio 301
Toxicidad G3/4
Estudio 305
Eribulina
Capecitabina
Eribulina
Control
Anemia
2%
1%
2-3%
4%
Neutropenia
46%
5%
45%
21%
Neutropenia febril
2%
1%
4%
1%
0.5%
1%
6%
6%
9%
10%
Neuropatía sensitiva
3.5%
0.5%
9%
2%
Alopecia
35%
4%
45%
10%
Naúseas
0.2%
1.6%
1%
2%
0%
14.5%
1.1%
5.3%
HEMATOLOGICA
Trombopenia
NO HEMATOLOGICA
Astenia/Fatiga
Sd Mano-pie
Diarrea
Eribulin: New approved clinical indication in EU(*)
HALAVEN monotherapy is indicated for the treatment of patients with
locally advanced or metastatic breast cancer who have progressed after
at least two one chemotherapeutic regimen for advanced disease (see
section 5.1). Prior therapy should have included an anthracycline and a
taxane in either the adjuvant or metastatic setting unless patients were
not suitable for these treatments
(*) SmPC approved by EMA in June 2014.
Platinos:
Nuevos datos clínicos
Antiangiogénicos:
Nuevos datos clínicos
Bevacizumab en 1ª línea CMM
Bevacizumab en 1ª línea CMM
Bevacizumab en 1ª línea CMM
IMELDA:
Open-label randomised phase III trial
3‒6 cycles
Previously
untreated
HER2-negative
LR/mBC
BEV 15 mg/kg +
DOC
75‒100 mg/m2
d1 q3w
BEV 15 mg/kg
d1 q3w
CR, PR
or SD
R
1:1
Stratification factors
• ER status (positive vs negative)
• Visceral metastasis (present vs absent)
• Stable disease/response/non-measurable disease
• LDH concentration (≤1.5 vs >1.5 × ULN)
BEV 15 mg/kg d1 +
CAP 1000 mg/m2 bid
d1‒14 q3w
CAP = capecitabine; CR = complete response; ER = oestrogen receptor; LDH = lactate dehydrogenase; PR = partial response;
SD = stable disease; R = randomisation; ULN = upper limit of normal.
Treat to PD,
unacceptable
toxicity or
withdrawal of
consent
Patient disposition
Enrolled (N=287)
Withdrawn before treatment (N=3)
Discontinued initial treatment
(N=99)
PD (N=41)
AE/toxicity (N=31)
Other reason (N=27)a
aWithdrew
consent/patient’s decision (N=13),
inclusion/exclusion criteria or protocol violation (N=5),
investigator/medical decision (N=4), health
authority/study termination (N=3), death (N=2)
Treated in initial phase
(N=284)
Completed initial treatment
and randomised (N=185)
R
BEV alone (N=94)
• Treated (N=92)
• Untreated (N=2)
AE = adverse event
BEV–CAP (N=91)
• Treated (N=91)
Primary endpoint:
PFS from time of randomisation
1.0
Estimated probability
Events, n (%)
0.8
Median PFS, months
(95% CI)
0.6
Stratified hazard ratio
(95% CI)
BEV
(N=94)
BEV–CAP
(N=91)
83 (88)
69 (76)
4.3
(3.9–6.8)
11.9
(9.8–15.4)
0.38
(0.27–0.55)
Stratified 2-sided log-rank test
p<0.0001
0.4
0.2
0
No. at risk
BEV–CAP
BEV
91
12
94
11.9
4.3
0
3
80
8
60
6
9
62
2
40
12
15 18
21 24
27 30
Time from randomisation (months)
50
2
20
40
1
17
34
0
11
33
36
39
42
26
22
16
9
6
2
PFS in prespecified subgroups
No. of events/patients (%)
Median PFS, months
Unstratified hazard ratio (95% CI)
BEV–CAP
BEV
BEV–CAP
BEV
Favours BEV–CAP
All (stratified)
69/91 (76)
83/94 (88)
11.9
4.3
Age <65 years
57/77 (74)
73/81 (90)
12.2
4.9
Age ≥65 years
12/14 (86)
10/13 (77)
11.7
4.3
Triple negative
19/25 (76)
21/21 (100)
7.6
3.3
Hormone receptor positive
50/66 (76)
62/73 (85)
13.0
6.1
ER positivea
48/64 (75)
59/69 (86)
14.1
4.9
ER negativea
21/27 (78)
24/25 (96)
7.6
3.8
<3 metastatic organ sites
39/48 (81)
33/40 (83)
10.4
6.2
≥3 metastatic organ sites
30/43 (70)
50/54 (93)
15.4
4.0
Visceral metastasesa
47/62 (76)
60/65 (92)
11.9
4.2
No visceral metastasesa
22/29 (76)
23/29 (79)
14.1
7.6
Responsea
53/68 (78)
59/68 (87)
11.9
4.2
Stable diseasea
13/20 (65)
21/22 (95)
19.3
4.9
LDH ≤1.5 × ULNa
64/85 (75)
78/89 (88)
12.4
4.3
LDH >1.5 × ULNa
5/6 (83)
5/5 (100)
3.0
4.1
Subgroup
aStratification
factors (data at randomisation)
Favours BEV
IMELDA:
OS from time of randomisation
BEV
(N=94)
BEV–CAP
(N=91)
53 (56)
33 (36)
1-year OS rate (%)
72
90
2-year OS rate (%)
49
69
Events, n (%)
1.0
Stratified hazard ratio
(95% CI)
Stratified 2-sided log-rank
0.8
Estimated probability
0.43
(0.26–0.69)
Median, months (95% CI)
p<0.0003
23.7
39.0
(18.5–31.7) (32.3–NR)
0.6
0.4
0.2
23.7
(95% CI: 18.5–31.7)
0
0
No. at risk
BEV–CAP
91
47
39.0
3
6
87
36
9
84
21
12
(95% CI 32.3–NR)
15 18 21 24 27 30 33
Time from randomisation (months)
78
10
72
4
70
0
64
0
36
39
60
42
45
54
Bevacizumab: biomarcadores predictivos
Miles D, ASCO 2013
Conclusiones
• Nuevas formulaciones: nab-placitaxel
- significativamente mejor que paclitaxel
en neoadyuvancia
Conclusiones
• Nuevas formulaciones: nab-placitaxel
- significativamente mejor que paclitaxel
en neoadyuvancia
• Nuevas formulaciones: Etirinotecan
- significativamente mejor que irinotecan
en algunos subgrupos
Conclusiones
• Nuevas formulaciones: nab-placitaxel
- significativamente mejor que paclitaxel
en neoadyuvancia
• Nuevas formulaciones: Etirinotecan
- significativamente mejor que irinotecan
en algunos subgrupos
• Nuevos antimicrotúbulos: Eribulina
- tras antraciclinas y taxanos como alternativa
a capecitabina
Conclusiones
• Platinos
- en fenotipo triple negativo, fundamentalmente
en basal like y BRCA mutado (línea germinal)
Conclusiones
• Platinos
- en fenotipo triple negativo, fundamentalmente
en basal like y BRCA mutado (línea germinal)
• Bevacizumab
- en esquema de mantenimiento con capecitabina
en pacientes respondedores a 1ª línea con taxano