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.

Bo

ne

Lo

ss a

t 1

Yr

(%)

Naturally Occurring Bone Loss CTIBL

0

2

4

6

8

10

Normal Men[1]

Postmenopausal Women[1]

Al Therapy inPostmenopausal

Women[2]

ADT[3]

Al Therapy+ GnRH

Agonist inPremenopausal

Women[4]

Premature Menopause

Secondary toChemotherapy[5]

0.51.0

2.6

4.6

7.07.7

Tamoxifen

LetrozoleAnastrozole

Fra

ctu

res

(%)

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 failureSaarto T, et al. J Clin Oncol. 1997;15:1341-1347.

• Risedronate reduces bone loss in women with chemotherapy-induced ovarian failureDelmas 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 lossLester 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 orFRAX 10-yr fracture risk: > 20% major fracture > 3% for hip fracture

• Repeat DXA every 2 yrs*

• Repeat DXA every 2 yrs*• Consider checking 25(OH) level

• Repeat DXA every 2 yrs*• Consider checking 25(OH) level• Consider pharmacologic

therapy• Repeat DXA every 2 yrs*• Consider checking 25(OH) level• 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 mosSecondary: BMD at 36 and 60 mos, disease recurrence, fractures, safety

Letrozole + immediate Zoledronic Acid 4 mg every 6 mos

Breast cancerstage I to IIIa(N = 1065)Postmenopausal or amenorrheic due to cancer treatmentER+ and/or PgR+

T-score ≥ -2.0

Letrozole +

Treatment duration: 5 yrs

RDelayed Zoledronic Acid

If 1 of the following occurs:BMD T-score < -2 Clinical fractureAsymptomatic 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 acidDelayed zoledronic acid

P < .0001 for each

Ch

ang

e in

LS

(L

S-L

4) B

MD

(%

)

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 conintolerancia GI (RGE) uotros 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-yrBMD

5-yrBMD

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

Per

cen

t C

han

ge

in L

S

BM

D (

g/c

m2 )

Fro

m B

asel

ine

Mos

Mos

No Zoledronic Acid

Tamoxifen Anastrozole

36 60

-9.0P < .0001

-4.5NS

-13.6P < .0001

-7.8P = .003

36 60

36 60 36 60

Zoledronic Acid

Tamoxifen Anastrozole

+1.0NS

+5.2P = .04

-0.1NS

+3.1NS

*

*

*

Ellis GK, et al. J Clin Oncol. 2008;26:4875-4882.

Denosumab in Patients With Breast Cancer Receiving Adjuvant AIs

Per

cen

t C

han

ge

in B

MD

Fro

m

Bas

elin

e at

LS

8

7

6

5

4

3

2

1

0

-1

-2

-31 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

ExerciseCalcium 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.

ExerciseTreatment 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 SOBREVIDALIBRE DE ENFERMEDAD?

Y/OSOBREVIDA GLOBAL?

DFS

ABCSG-12 (84 Mos): Efficacy

100

80

60

40

20

0

DF

S (

%)

0 12 24 36 48 60 72 84 96 108

Mos Since RandomizationPatients at Risk, nNo ZAZA

903900

858862

833841

807822

758788

653674

521544

405419

191208

Events, n

Univariate Multiple CoxRegression

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

DF

S (

%)

0 12 24 36 48 60 72 84 96 108

Mos Since RandomizationPatients at Risk, nNo ZAZA

903900

864868

856858

839849

811818

706708

576587

456454

215232

Events, n

Univariate Multiple CoxRegression

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 DesignAccrual 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

Thailand 2 25

Taiwan 2 13

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 dosesq3-4w

8 dosesq3m

5 dosesq6m

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

ZAControl

0

Patients at Risk, n1681 1578 1443 1337 1222 570 821678 1574 1426 1316 1221 544 68

IDFS

0

ZAControl

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)

Su

rviv

ing

(%

)

00

ZA (n = 1681)

0

100100

00 1 2 3 4 5 6 7

20

40

60

80

Yrs

Su

rviv

ing

(%

)

00

100

00

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

Mos Since Randomization

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

Pro

po

rtio

n A

live

and

in

vasi

ve D

isea

se F

ree

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, nZA:

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

Pro

po

rtio

n A

live

OS: Pre, Peri, and Unknown Menopausal Status



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

Pro

po

rtio

n A

live

and

in

vasi

ve D

isea

se F

ree

IDFS: > 5 Yrs Postmenopausal



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

Pro

po

rtio

n A

live

OS: > 5 Yrs Postmenopausal



No ZA:519 502 482 448 422 190 29 0

522 509 475 441 401 177 26 0


Typical ORMenopausal Group

Description

Total: -1% ± 7%Z = .13; P = .9

21 (heterogeneity) = 7.91; P = .005

Odds Reduction (± SD)

n = 1041263 events

n = 2318544 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)

532533

518511

500491

488475

475463

376368

IM-ZAD-ZA

Patients at Risk, nTime on Study (mos)

532533

518459

500402

488376

475350

376267

IM-ZAD-ZA

Patients at Risk, n

ITT Population

100

90

80

70

60

50

40

30

20

10

0

DF

S (

%)

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

0D

FS

(%

)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 = 1041AZURE - > 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 withstage I-II breast cancer

receiving adjuvant standard therapy


R

Median follow-up: 8.4 yrsTwo thirds aged > 50 yrs; 25% N positive

NSABP B-34: DFS

Paterson A, et al. SABCS 2011. Abstract S2-3.

Dis

ease

Fre

e (%

)

100

80

60

40

20

00 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:

Epirubicin150 mg/m2

q2w

Ibandronate50 mg PO QD 2 yrs

Paclitaxel225 mg/m2

q2w

Cyclophosphamide2000 mg/m2

q2w

Arm B2:Observation

Arm A2:Paclitaxel67.5 mg/m2 qwCapecitabine2000 mg/m2 Days 1-14 q3w

Epirubicin112.5 mg/m2

Cyclophosphamide600 mg/m2 q2w

PegfilgrastimCiprofloxacin

Darbepoetin alfa or Epoetin beta

CiprofloxacinPegfilgrastim

Darbepoetin alfa or Epoetin beta

GAIN: DFS and OS (ITT)

1.0

0.8

0.6

0.4

0.2

0

Su

rviv

al P

rob

abil

ity

(%)

DFS (Mos)0 12 24 36 48 60

12

1996998

1814871

1590727

1057483

555264

210105

3-Yr DFSIbandronate: 87.6%Observation: 87.2%

Cox RegressionHR: 0.945 (95% CI: 0.768-1.16; P = .59)

Ibandronate Observation

Product-Limit Survival EstimatesWith Number of Patients at Risk

+ Censored1.0

0.8

0.6

0.4

0.2

0.0

OS (Mos)0 12 24 36 48 60

12

1996998

1836886

1653756

1121506

586277

219112

3-Yr OSIbandronate: 94.7%Observation: 94.1%

Cox RegressionHR: 1.04 (95% CI: 0.763-1.42; P = .80)

Product-Limit Survival EstimatesWith Number of Patients at Risk

+ Censored


GAIN: Subgroup AnalysesDFS for Ibandronate in Subgroups

HR0.5 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)


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

0Pat

ien

ts W

ith

ou

t E

ven

t (%

)

0 1 2 3 4 5 0

Yrs

P = .0003

Osteoporosis/no osteoporosis therapyOsteoporosis/osteoporosis therapyNo osteoporosis/no osteoporosis therapyNo 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 ClassRecommended 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 ofMedian Mos

DenosumabZoledronic acid

Not reached26.4

HR: 0.82 (95% CI: 0.71-0.95; P < .001 noninferiority; P = .01 superiority*)

Mos

0

1.00

Pro

po

rtio

n o

f S

ub

ject

s W

ith

ou

t S

RE

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)

Per

cen

t o

f S

ub

ject

s W

ith

SR

Es

(95%

CI)

4.5%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

GRACIAS

Cáncer de Mama

Health & Medicine

Transcript of Cáncer de Mama