Cáncer de Mama

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Cáncer de Mama

  1. 1. CÁNCER DE MAMA TERÁPIAS ÓSEAS
  2. 2. CA DE MAMA TEMPRANO: PREVENCIÓN DE FX AUMENTO DE LA SLE CON TERAPIAS ADYUVANTES ÓSEAS ENFERMEDAD METASTASICA
  3. 3. 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
  4. 4. 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
  5. 5. 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.
  6. 6. 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.
  7. 7. 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* • 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.
  8. 8. 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
  9. 9. 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
  10. 10. 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.
  11. 11. 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.
  12. 12. 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
  13. 13. * * * 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
  14. 14. 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.
  15. 15. 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.
  16. 16. ¿AUMENTAR LA SOBREVIDA LIBRE DE ENFERMEDAD? Y/O SOBREVIDA GLOBAL?
  17. 17. 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 Mos Since Randomization 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.
  18. 18. 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
  19. 19. 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) Coleman RE, et al. N Engl J Med. 2011;365:1396-1405.
  20. 20. 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 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 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 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 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 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 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 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 Coleman RE, et al. N Engl J Med. 2011;365:1396-1405.
  21. 21. 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 Coleman RE, et al. N Engl J Med. 2011;365:1396-1405.
  22. 22. 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
  23. 23. 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
  24. 24. 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 Treatment duration: 5 yrs De Boer R, et al. SABCS 2011. Abstract S1-3. ZO-FAST: 5-yr Final Analysis
  25. 25. *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
  26. 26. 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
  27. 27. 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 Treatment duration: 3 yrs R Median follow-up: 8.4 yrs Two thirds aged > 50 yrs; 25% N positive
  28. 28. 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
  29. 29. 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 Paterson A, et al. SABCS 2011. Abstract S2-3.
  30. 30. 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 Paterson A, et al. SABCS 2011. Abstract S2-3. DMFI: distant metastasis-free interval RFI: relapse-free interval BMFI: bone-metastasis-free interval NBMFI: non-bone metastasis-free interval
  31. 31. 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
  32. 32. 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 Möbus V, et al. SABCS 2011. Abstract S2- 4.
  33. 33. 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) Möbus V, et al. SABCS 2011. Abstract S2- 4.
  34. 34. 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.
  35. 35. 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.
  36. 36. 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
  37. 37. 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
  38. 38. 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.
  39. 39. 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. 40. 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
  41. 41. GRACIAS

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