Cáncer de Mama

CÁNCER DE MAMA
TERÁPIAS ÓSEAS

CA DE MAMA TEMPRANO: PREVENCIÓN DE FX
AUMENTO DE LA SLE CON TERAPIAS
ADYUVANTES ÓSEAS
ENFERMEDAD METASTASICA

Predictors of Fracture Risk
• BMD (DXA), femoral neck T-score
– Serial monitoring should be done on the same
equipment with the same reference standards at the
same site
• Age
• Drugs
• History/presence of vertebral fracture
– Best predictor of a subsequent fracture is an existing
one
• Risk of falls
• Vitamin D levels

Tasa de Pérdida Ósea
1. Kanis JA. Osteoporosis. 1997:22-55. 2. Eastell R, et al. J Bone Miner Res. 2006;21:1215-1223.
3. Maillefert JF, et al. J Urol. 1999;161:1219-1222. 4. Gnant M, et al. Lancet Oncol. 2008;9:840-849.
5. Shapiro CL, et al. J Clin Oncol. 2001;19:3306-3311.
BoneLossat1Yr(%)
Naturally Occurring Bone Loss CTIBL
0
2
4
6
8
10
Normal
Men[1]
Postmenopausal
Women[1]
Al Therapy in
Postmenopausal
Women[2]
ADT[3]
Al Therapy
+ GnRH
Agonist in
Premenopausal
Women[4]
Premature
Menopause
Secondary to
Chemotherapy[5]
0.5
1.0
2.6
4.6
7.0
7.7

Tamoxifen
LetrozoleAnastrozole
Fractures(%)
11.0
7.7
5.7
4.0
7.0
5.0
P < .0001
P < .001
0
2
4
6
8
10
12
14
P = .003
Exemestane
ATAC[1]
(68 mos)
IES[2]
(58 mos)
BIG 1-98[3]
(26 mos)
Riesgo de fx elevado de los IA esteroidales y
noesteroidales vs Tamoxifeno
1. Howell A, et al. Lancet. 2005;365:60-62. 2. Coleman RE, et al. Lancet Oncol. 2007;8:119-127.
3. Thürlimann B, et al. N Engl J Med. 2005;353:2747-2757.

Oral Bisphosphonate Impact on BMD
in Patients With Breast Cancer
• Clodronate in breast cancer patients with chemotherapy-induced
premature ovarian failure
Saarto T, et al. J Clin Oncol. 1997;15:1341-1347.
• Risedronate reduces bone loss in women with chemotherapy-
induced ovarian failure
Delmas PD, et al. J Clin Oncol. 1997;15:955-962.
• Alendronate in GnRH agonist-induced premature menopause
(patients without cancer)
Ripps BA, et al. J Reprod Med. 2003;48:761-766.
• Monthly ibandronate and anastrozole-induced bone loss
Lester JE, et al. Clin Cancer Res. 2008;14:6336-6342.
• SABRE trial: study of anastrozole with risedronate
Van Poznak C, et al. J Clin Oncol. 2010;28:967-975.

Management of Bone Health Using
BMD
T-Score: NCCN Task Force Report
• T-score: > -1 (normal)
• T-score: -1.0 to -1.5
• T-score: -1.5 to -2.0
• T-score < -2.0 or
FRAX 10-yr fracture risk:
> 20% major fracture
> 3% for hip fracture
• Repeat DXA every 2 yrs*
• Consider checking 25(OH) level
• Consider pharmacologic
therapy
• Strongly consider
pharmacologic therapy
Gralow JR, et al. J Natl Compr Canc Netw. 2009;7:S1-S32.
*In selected cases, longer or shorter intervals may be considered. If a major change in patient risk
factors or a major intervention occurs, then repeating DXA at 1 yr is reasonable.

Key endpoints:
Primary: BMD at 12 mos
Secondary: BMD at 36 and 60 mos, disease recurrence, fractures, safety
Letrozole +
immediate Zoledronic Acid
4 mg every 6 mos
Breast cancer
stage I to IIIa
(N = 1065)
Postmenopausal or
amenorrheic due to
cancer treatment
ER+
and/or PgR+
T-score ≥ -2.0
Letrozole +
Treatment duration: 5 yrs
R
Delayed Zoledronic Acid
If 1 of the following occurs:
BMD T-score < -2
Clinical fracture
Asymptomatic fracture at
36 mos
Coleman R, et al. Ann Oncol. 2012. Oct 9.
ZO-FAST: A Phase III Study of the Use of
Zoledronic Acid With Adjuvant Letrozole

Coleman R, et al. Ann Oncol. 2012. Oct 9. [Epub ahead of print]
ZO-FAST (Primary Endpoint): Median
Change in LS BMD With Zoledronic Acid
Immediate zoledronic acid
Delayed zoledronic acid
P < .0001 for each
ChangeinLS(LS-L4)BMD(%)
12 Mos 24 Mos 36 Mos 48 Mos 60 Mos-6
-4
-2
0
2
4
6
+4.3
-5.4
Δ 5.9 Δ 8.2 Δ 8.8 Δ 9.2 Δ 10.0

Modalidades de tratamiento
Bifosfonatos orales
• Buena adherencia a sus
meds
• Rechazan meds IV
• No quieren o pueden ir a
la clínica
• Menos costosos
• Menos efectos 2os
• < riesgo de osteonecrosis
o de fx subtrocantéricas
Bifosfonatos IV
• Mayor adherencia en
pacientes con
intolerancia GI (RGE) u
otros síntomas.

ABCSG-12: Phase III Study of Adjuvant
Endocrine Therapy ± Zoledronic Acid
• Key endpoints
– Primary: DFS at 5 yrs
– Secondary: recurrence-free survival, OS, BMD, safety
TAM 20 mg/day
ANA 1 mg/day
Treatment 3 yrs
(median follow-up: 48 mos)
TAM + ZA 4 mg q6m
ANA + ZA 4 mg q6m
R
Long-term
monitoring
for 5 yrs for
recurrence
and survival
(DFS, OS)
3-yr
BMD
5-yr
BMD
Premenopausal patients with
stage I/II breast cancer
(goserelin 3.6 mg/28 days)
stratified by:
 ER+ and/or PgR+
 Age
 Stage
 Grade
 Lymph nodes
(N = 1803)
Gnant M, et al. N Engl J Med. 2009;360:679-691.

Gnant M, et al. Lancet Oncol. 2008;9:840-849.
ABCSG-12 Bone Substudy: Change in
BMD at Yrs 3 and 5
10
5
0
-5
-10
-15
PercentChangeinLS
BMD(g/cm2
)FromBaseline
Mos
Mos
No Zoledronic Acid
Tamoxifen Anastrozole
36 60
-9.0
P < .0001
-4.5
NS
-13.6
P < .0001
-7.8
P = .003
36 60
36 60 36 60
Zoledronic Acid
Tamoxifen Anastrozole
+1.0
NS
+5.2
P = .04
-0.1
NS
+3.1
NS

*
*
*
Ellis GK, et al. J Clin Oncol. 2008;26:4875-4882.
Denosumab in Patients With Breast
Cancer Receiving Adjuvant AIsPercentChangeinBMDFrom
BaselineatLS
8
7
6
5
4
3
2
1
0
-1
-2
-3
1 3 6 12 24
Mos
5.5% difference
at 12 mos
7.6% difference
at 24 mos
*P < .0001 vs placebo
Placebo (n = 122)
Denosumab 60 mg q6m (n = 123) *
*
Toxicity: no significant difference in AEs between denosumab and placebo arm

Checklist for Bone Health in Patients With
Breast Cancer
Item Description
Determine
osteoporosis risk
factors
•T-score < -1.5?
•Older than 65 yrs?
•Low BMI (< 20)?
Other factors
•Family history of hip fracture?
•Personal history of fragility after 50 yrs of age?
•Oral corticosteroid use of > 6 mos?
•Smoking (current or past history)?
•10-yr probability for hip fracture (by FRAX)?
Cancer treatment–
related factors
•AIs?
•Ovarian ablation?
Assays
•DXA to assess BMD (every 2 yrs)
•25(OH)D level
•Serum calcium level
Treat the following
with bone-directed
therapy
•Hip or vertebral fracture
•T-score < -2.0
•10-yr probability for hip fracture ≥ 3%
•10-yr probability of a major osteoporotic event ≥ 20%
Hadji P, et al. Ann Oncol. 2011;22:2546-2555. National Osteoporosis Foundation.

T-score < -2.0Any 2 of the following risk factors
 T-score < -1.5
 Aged younger than 65 yrs
 Low BMI (< 20)
 Family history of hip fracture
 Personal history of fragility fracture after
50 yrs of age
 Oral corticosteroid use of > 6 mos
 Smoking (current or history of)
T-score > -2.0, no risk
factors
Monitor risk status and
BMD q12m*
Monitor BMD on case by case
basis for IV bisphosphonates;
q12-24m for oral
bisphosphonates
Exercise
Calcium and vitamin D
supplements
*If ≥ 10% decrease in BMD (≥ 4% to 5% if osteopenic at baseline),
investigate secondary causes and begin antiresorptive treatment. Use lowest T-score from 3 sites.
Exercise
Treatment including
bisphosphonates,
denosumab,
Calcium, and vitamin D
supplements
Guidance for Women With Breast
Cancer Initiating AI Therapy: European
Guidelines
Hadji P, et al. Ann Oncol. 2011;22:2546-2555.

¿AUMENTAR LA SOBREVIDA
LIBRE DE ENFERMEDAD?
Y/O
SOBREVIDA GLOBAL?

DFS
ABCSG-12 (84 Mos): Efficacy
100
80
60
40
20
0
DFS(%)
0 12 24 36 48 60 72 84 96 108
Mos Since Randomization
Patients at Risk, n
No ZA
ZA
903
900
858
862
833
841
807
822
758
788
653
674
521
544
405
419
191
208
Events,
n
Univariate Multiple Cox
Regression
HR
(95% CI)
P
Value
HR
(95% CI)
P
Value
vs no
ZA
vs no
ZA
(Log-
rank)
No
ZA
132/903
0.72
(0.56-0.94)
.014 0.71
(0.55-0.92)
.01198/900ZA
OS
100
80
60
40
20
0
DFS(%)
0 12 24 36 48 60 72 84 96 108
Patients at Risk, n
No ZA
ZA
903
900
864
868
856
858
839
849
811
818
706
708
576
587
456
454
215
232
Events,
n
Univariate Multiple Cox
Regression
HR
(95% CI)
P
Value
HR
(95% CI)
P
Value
vs no
ZA
vs no
ZA
(Log-
rank)
No
ZA
49/903
0.63
(0.40-0.99)
.049 0.61
(0.39-0.96)
.03333/900ZA
Gnant M, et al. SABCS 2011. Abstract S1-2.

ZA treatment duration: 5 yrs
AZURE: Study Design
Accrual September 2003 - February 2006
Country Centers,
n
Patients, n
United
Kingdom
123 2710
Ireland 10 247
Australia 28 226
Spain 8 107
Portugal 1 32
Coleman RE, et al. N Engl J Med. 2011;365:1396-1405.
Standard therapy
Standard therapy +
ZA 4 mg
Mos 6 30 60
3360 patients
with stage II/III
breast cancer
R
6 doses
q3-4w
8 doses
q3m
5 doses
q6m
 Primary endpoint: DFS, with recurrence
defined as date first suspected

AZURE: DFS and IDFS
Patients at Risk, n
1681 1591 1465 1354 1241 580 83
1678 1583 1445 1344 1252 561 71
DFS
0
ZA
Control
0
Patients at Risk, n
1681 1578 1443 1337 1222 570 82
1678 1574 1426 1316 1221 544 68
IDFS
0
ZA
Control
DFS IDFS
1 2 3 4 5 6 7
20
40
60
80
Yrs
Control (n = 1678)
Adjusted HR: 0.98 (95% CI: 0.85-1.13;
P = .79)
Surviving(%)
0
0
ZA (n = 1681)
0
100100
0
0 1 2 3 4 5 6 7
20
40
60
80
Yrs
Surviving(%)
0
0
100
0
0
Control (n = 1678)
Adjusted HR: 0.98 (95% CI: 0.85-1.12;
P = .73)
ZA (n = 1681)

AZURE: IDFS and OS by
Menopausal Status
0
1.0
6 12 18 24 30 36 42 48 54 60 66 72 78 84
0.8
0.6
0.4
0.2
0
ProportionAliveand
invasiveDiseaseFree
IDFS: Pre, Peri, and Unknown Menopausal Status
Adjusted HR: 1.15
(95% CI: 0.97-1.36; P = .11)
288 vs 256 events
Patients at Risk, n
ZA:
No ZA:
1162 1088 996 919 829 393 57 0
1156 1092 995 920 853 388 47 0
0
1.0
6 12 18 24 30 36 42 48 54 60 66 72 78 84
0.8
0.6
0.4
0.2
0
ProportionAlive
OS: Pre, Peri, and Unknown Menopausal Status
Adjusted HR: 0.97
(95% CI: 0.78-1.21; P = .81)
161 vs 165 events
Patients at Risk, n
ZA:
No ZA:
1162 1131 1078 1020 955 466 71 0
1156 1123 1076 1032 963 446 60 0
0
1.0
6 12 18 24 30 36 42 48 54 60 66 72 78 84
0.8
0.6
0.4
0.2
0
ProportionAliveand
invasiveDiseaseFree
IDFS: > 5 Yrs Postmenopausal
Adjusted HR: 0.75
(95% CI: 0.59-0.96; P = .02)
116 vs 147 events
Patients at Risk, n
ZA:
No ZA:
519 490 447 418 393 177 25 0
522 482 431 396 368 156 21 0
0
1.0
6 12 18 24 30 36 42 48 54 60 66 72 78 84
0.8
0.6
0.4
0.2
0
ProportionAlive
OS: > 5 Yrs Postmenopausal
Adjusted HR: 0.74
(95% CI: 0.55-0.98; P = .04)
82 vs 111 events
Patients at Risk, n
ZA:
No ZA:
519 502 482 448 422 190 29 0
522 509 475 441 401 177 26 0

Typical OR
Menopausal Group
Description
Total: -1% ± 7%
Z = .13; P = .9
χ2
1 (heterogeneity) = 7.91; P = .005
Odds Reduction (± SD)
n = 1041
263 events
n = 2318
544 events
HR: 0.75
(95% CI: 0.59-0.96)
HR: 1.15
(95% CI: 0.97-1.36)
Pre + < 5 yrs post
+ unknown status
> 5 yrs postmenopausal
High estrogen
environment
Low estrogen
environment
1.0 1.2 1.4 1.6 1.8 2.00.2 0.4 0.6 0.8
AZURE: Treatment Effect on IDFS
by Menopausal Status

Niveles de Vit D 25 OHD > 30 ng/ml (suficientes)
predicen beneficio del Ac Zoledrónico en las
tasas de recidiva a distancia en pacientes
posmenopausicas

Marshall H, et al. ASCO 2012. Abstract 502.
Adjuvant Zoledronic Acid in Early Breast
Cancer: Expert Perspectives
• No benefit in overall unselected population
• Significant benefit in postmenopausal women seen in
multiple studies
– Effect of menopause on DFS driven by influences on
nonbone recurrence
• Potential for harm in pre- and perimenopausal women
• These subset analyses do not justify the routine use of
adjuvant zoledronic acid in postmenopausal women

Letrozole +
ZA 4 mg q6m
Letrozole + Delayed*
ZA 4 mg q6m
*If 1 of the following occurs:
BMD T-score < -2 SD
Clinical fracture
Asymptomatic fracture at 36 mos
Stage I-IIIa breast cancer
 Postmenopausal or
amenorrheic due to
cancer treatment
 ER+ and/or PgR+
 T-score ≥ -2 SD
N = 1060
De Boer R, et al. SABCS 2011. Abstract S1-3.
ZO-FAST: 5-yr Final Analysis

*Censored patients at initiation of D-ZA (n = 144).
Time on Study (mos)
532
533
518
511
500
491
488
475
475
463
376
368
IM-ZA
D-ZA
Patients at Risk, n
Time on Study (mos)
532
533
518
459
500
402
488
376
475
350
376
267
IM-ZA
D-ZA
Patients at Risk, n
ITT Population
100
90
80
70
60
50
40
30
20
10
0
DFS(%)
0 6 12 18 24 30 36 42 48 54 60 66
HR: 0.66; log-rank P value = .0375
IM-ZA 4 mg (42 events)
D-ZA 4 mg (62 events)
Censored Analysis*
100
90
80
70
60
50
40
30
20
10
0DFS(%)
0 6 12 18 24 30 36 42 48 54 60 66
HR: 0.62; log-rank P value = .024
IM-ZA 4 mg (42 events)
D-ZA 4 mg (53 events)
De Boer R, et al. SABCS 2011. Abstract S1-3.
27% of patients (n = 144) in the delayed arm initiated ZA on-study
DFS HR: 0.46; P = .033
ZO-FAST: Final 5-yr DFS

HR
ZO-FAST[1]
 104 events
ABCSG-12[3]
 230 events
0.2 0.4 0.6 0.8 1 1.2 1.4
N = 1803
1. De Boer R, et al. SABCS 2011. Abstract S1-3. 2. Coleman RE, et al. N Engl J Med. 2011;365:1396-
1405. 3. Gnant M, et al. SABCS 2011. Abstract S1-2.
N = 1065
n = 1041
AZURE - > 5 yrs postmenopausal[2]
 263 events
P Value
.02
.0375
.011
0.75
0.66
0.71
ZA Studies: DFS Comparison

NSABP B-34: Phase III Study of
Adjuvant Clodronate in Breast Cancer
• Primary endpoint: DFS
• Secondary endpoints: incidence of metastases, OS,
SREs, adverse events, and prognostic serum markers
Clodronate
1600 mg qd
Placebo
3323 patients with
stage I-II breast cancer
receiving adjuvant
standard therapy
R
Median follow-up: 8.4 yrs
Two thirds aged > 50 yrs; 25% N positive

NSABP B-34: DFS
Paterson A, et al. SABCS 2011. Abstract S2-3.
DiseaseFree(%)
100
80
60
40
20
0
0 2 4 6 8
Yrs After Randomization
Treatment
Placebo
Clodronate
N
1656
1655
Events, n
312
286
HR: 0.91; P = .27

NSABP B-34: Analysis of
Specified Endpoints and Safety
• Adverse events comparable in clodronate and placebo arms
– 1 case of ONJ observed in clodronate arm vs no cases in placebo
arm
Endpoint Events, n HR (95% CI) P Value
Clodronate
(n = 1662)
Placebo
(n = 1661)
DFS 286 312 0.913 (0.778-1.072) .266
OS 140 167 0.842 (0.672-1.054) .131
RFI 148 177 0.834 (0.671-1.038) .101
BMFI 61 80 0.765 (0.548-1.068) .114
NBMFI 78 105 0.743 (0.554-0.996) .046

NSABP B-34 Subset Analysis: DMFI,
RFI, BMFI, and NBMFI in Patients ≥ 50
Yrs
Endpoint for Patients 50
Yrs of Age or Older
HR P Value
DMFI 0.62 .003
RFI 0.76 .05
BMFI 0.61 .024
NBMFI 0.63 .015
DMFI: distant metastasis-free interval
RFI: relapse-free interval
BMFI: bone-metastasis-free interval
NBMFI: non-bone metastasis-free interval

GAIN Trial: Study Design
Möbus V, et al. SABCS 2011. Abstract S2-
4.
Arm A1: Arm B1:
Epirubicin
150 mg/m2
q2w
Ibandronate
50 mg PO QD 2 yrs
Paclitaxel
225 mg/m2
q2w
Cyclophosphamide
2000 mg/m2
q2w
Arm B2:
Observation
Arm A2:
Paclitaxel
67.5 mg/m2
qw
Capecitabine
2000 mg/m2
Days 1-14 q3w
Epirubicin
112.5 mg/m2
Cyclophosphamide
600 mg/m2
q2w
Pegfilgrastim
Ciprofloxacin
Darbepoetin alfa or Epoetin beta
Ciprofloxacin
Pegfilgrastim
Darbepoetin alfa or Epoetin beta

GAIN: DFS and OS (ITT)
1.0
0.8
0.6
0.4
0.2
0
SurvivalProbability(%)
DFS (Mos)
0 12 24 36 48 60
1
2
1996
998
1814
871
1590
727
1057
483
555
264
210
105
3-Yr DFS
Ibandronate: 87.6%
Observation: 87.2%
Cox Regression
HR: 0.945 (95% CI: 0.768-1.16; P = .
59)
Ibandronate Observation
Product-Limit Survival Estimates
With Number of Patients at Risk
+ Censored
1.0
0.8
0.6
0.4
0.2
0.0
OS (Mos)
0 12 24 36 48 60
1
2
1996
998
1836
886
1653
756
1121
506
586
277
219
112
3-Yr OS
Ibandronate: 94.7%
Observation: 94.1%
Cox Regression
HR: 1.04 (95% CI: 0.763-1.42; P = .80)
Product-Limit Survival Estimates
With Number of Patients at Risk
+ Censored
4.

GAIN: Subgroup Analyses
DFS for Ibandronate in Subgroups
HR
0.5 1.0 1.5
Better With Ibandronate Worse With Ibandronate
pN1
pN2
pN3
ER and/or PgR positive
ER and PgR negative
Pre- and perimenopausal
Postmenopausal
< 60 yrs
≥ 60 yrs
HR: 1.04 (95% CI: 0.652-1.65; P = .877)
HR: 0.875 (95% CI: 0.599-1.28; P = .490)
HR: 0.951 (95% CI: 0.710-1.27; P = .734)
HR: 0.952 (95% CI: 0.736-1.23; P = .706)
HR: 0.856 (95% CI: 0.604-1.21; P = .383)
HR: 1.02 (95% CI: 0.756-1.37; P = .912)
HR: 0.897 (95% CI: 0.671-1.20; P = .462)
HR: 1.02 (95% CI: 0.807-1.30; P = .842)
HR: 0.746 (95% CI: 0.490-1.14; P = .172)
4.

Variable Efficacy in
an Unselected Population
*Analysis relates to bone metastasis-free survival.
1. Coleman RE, et al. N Engl J Med. 2011;365:1396-1405. 2. Gnant M, et al. SABCS 2011. Abstract S1-2.
3. De Boer R, et al. SABCS 2011. Abstract S1-3. 4. Paterson A, et al. SABCS 2011. Abstract S2-3.
5. Powles T, et al. Breast Cancer Res. 2006;8:R13. 6. Mobus V, et al. SABCS 2011. Abstract S2-4.

Consistent Efficacy in
“Postmenopausal” Women
*Includes patients > 40 yrs on goserelin; no significant effect for patients < 40 yrs.
†
Analysis relates to OS.
‡
≥ 60 yrs at study entry.
1. Coleman RE, et al. N Engl J Med. 2011;365:1396-1405. 2. Gnant M, et al. SABCS 2011. Abstract S1-2.
3. De Boer R, et al. SABCS 2011. Abstract S1-3. 4. Paterson A, et al. SABCS 2011. Abstract S2-3.
5. Powles T, et al. Breast Cancer Res. 2006;8:R13. 6. Mobus V, et al. SABCS 2011. Abstract S2-4.

Conclusions
• Targeting the host environment may complement activity
of direct anticancer treatments
• Adjuvant benefit from bone-targeted treatment appears to
be dependent on a low reproductive hormone environment
– Biologic mechanisms need further evaluation
• Inhibiting the vicious cycle may not always be beneficial
• Adjuvant ZA should be considered in women with a low
estrogen environment
– Prevent bone loss and fragility fracture
– Potentially improve disease outcomes

Shepherd LE, et al. ASCO 2012. Abstract 501. Used with permission.
Exemestane vs Anastrozole in Early Breast
Cancer (MA.27): EFS Analysis
• EFS significantly improved with vs without osteoporosis therapy
(HR: 0.70; P < .00001)
Patient-
Reported
Outcome,
n (%)
Osteoporosis
Yes
(n =
1294)
No
(n =
6282)
Osteoporosis
therapy
(n = 2711)
1101
(85)
1610
(25.6)
No
osteoporosis
therapy
(n = 4865)
193
(15)
4672
(74.4)
100
80
0
PatientsWithoutEvent(%)
0 1 2 3 4 5 0
Yrs
P = .0003
Osteoporosis/no osteoporosis therapy
Osteoporosis/osteoporosis therapy
No osteoporosis/no osteoporosis therapy
No osteoporosis/osteoporosis therapy

FDA-Approved Antiosteoclast Agents for
Reduction of SREs in MBC
• Both ASCO and NCCN recommend all 3 agents
• No agent recommended over another
Agent Drug Class
Recommended Dose and
Schedule
Zoledronic
acid
Bisphosphonate 4 mg IV q3-4w
Pamidronate Bisphosphonate 90 mg IV q3-4w
Denosumab RANKL-targeted MAb 120 mg SQ q4w
1. Van Poznak CH, et al. J Clin Oncol. 2011;29:1221-1227. 2. National Comprehensive Cancer Network.
Clinical practice guidelines in oncology: breast cancer. v.1.2012.

Denosumab vs Zoledronic Acid: Time to
First On-Study SRE
Zoledronic acid 1020 829 676 584 498 427 296 191 94 29
Denosumab 1026 839 697 602 514 437 306 189 99 26
Patients at Risk, n
KM Estimate of
Median Mos
Denosumab
Zoledronic acid
Not reached
26.4
HR: 0.82 (95% CI: 0.71-0.95; P < .001
noninferiority; P = .01 superiority*)
Mos
0
1.00
ProportionofSubjects
WithoutSRE
0 3 6 9 12 15 18 21 24 27 30
0.25
0.50
0.75
Stopeck AT, et al. J Clin Oncol. 2010;28:5132-5139.

40
20
0
Mo 12 Mo 18 At Time of Analysis
Denosumab (n = 1026)Zoledronic acid (n = 1020)
PercentofSubjects
WithSREs(95%CI)
4.5%
relative reduction
11.4%
relative reduction
15.4%
relative reduction
10
30
28.8%32.5% 32.9%38.9%25.4%26.6%
Stopeck A, et al. SABCS 2010. Abstract P6-14-01.
Denosumab vs Zoledronic Acid: Proportion
Experiencing ≥ 1 SRE

Cáncer de Mama

More Related Content

What's hot (19)

Viewers also liked (7)

Similar to Cáncer de Mama (20)

More from Consejo Panameño de Osteopososis (15)

Recently uploaded (20)

Cáncer de Mama