T. Cufer - Breast cancer - State of the art for advanced breast cancer

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T. Cufer - Breast cancer - State of the art for advanced breast cancer

  1. 1. Metastatic BreastCancer Treatment:State of the Art Tanja Cufer, MD, PhD University Clinic Golnik Medical Faculty, Ljubljana EORTC BCG, ChairESO Masterclass; Amman 2011
  2. 2. Metastatic Breast Cancer (MBC) The survival of pts with 5-year survival of MBC pts in metastatic disease is Slovenia improving MBC is still: 20 18  Incurable but highly 16 treatable 14 1980-85 1986-90  Chronic disease 12 Survival (%) 1990-95 10 The goal of treatment: 8 1996-00 2000-05  Control of symptoms 6 4  Prolongation of life 2  Good quality of life 0
  3. 3. Multidisciplinary Treatment Modalitiesin MBC Systemic therapy  Endocrine therapy  Chemotherapy  Targeted systemic therapy Radiotherapy (bone, CNS mets) Surgery (solitary lesions) Supportive therapy (bisphosphonates) Palliative medicine
  4. 4. 1st main question:Optimal systemic therapy in first- line treatment?
  5. 5. Tailoring Systemic Therapy in MBC  Disease-related factors  Biology of disease  ER/PR status  HER2 status  Proliferation  Disease-free interval  Tumor burden (number & site of mets)  Need for rapid disease control  Previous systemic therapy  Patient-related factors  PS  Age  Co-morbidities  Patient’s preferences
  6. 6. Individualized Treatment SelectionHER2 Endocrine responsive Endocrine non-responsive (HR+, long DFI, soft (HR-/uncertain, short DFI, ER tissue/bone mets) visceral mets)HER2- ET CTnegativeHER2- positive HER2 directed + ET HER2-directed + CT Thargeted therapies comes first!
  7. 7. 2nd main question:Repeating ER/PR and HER2 status at the time of progression?
  8. 8. ASCO 2010: Significant Rate of Discordance Between Primary and Metastases #1007 #CRA 1008 #1009 Studies Amir et al. Locatelli et al. Karlsson et al. N=271 N=255 N=477 prospective retrospective retrospective (liver) Would you deny a(12%) 22/197 (11%) 123/336 (36%)ER+ primary with loss in recurrence 21/174 patient a targetedER- primary with gain in recurrence 8/57 (14%) 15/58 (25%) 32/141 (22%) treatment due to changes in the 32%Overall ER discordance rate 12% 14.5%Overall PR discordance ratemetastatic site? 48% 34% 43%HER2- primary with gain in recurrence 9/197 (4.6%) 7/118 (5.9%) n.d.HER2+ primary with loss in recurrence 3/24 (12.5%) 17/54 (31.5%) n.d.Change in management from results of 15% 12% n.d.recurrence biopsyDiscussion ASCO 2010: Richardson AL
  9. 9. Endocrine Therapy for MBC Premenopausal patients  Tamoxifen  OAS  OAS +Tamoxifen  OAS + AI Postmenopausal patients  Als  Tamoxifen  Fulvestrant
  10. 10. Combined Tamoxifen and LHRH Agonist vs LHRH Agonist Alone in Premenopausal Advanced Breast Cancer: A Meta-Analysis of Four Randomized Trials End Point LHRH agonist LHRH agonist HR 95%CI p alone + Tamoxifen N=256 N=250Median survival, years 2.5 2.9 0.78 0.63-0.96 0.02Median PFS, months 5.4 8.7 0.70 0.58-0.85 0.0003Objective response % 29.7 38.8 0.67 0.46-0.96 0.03 LHRH+TAM LHRHKlijn, et al. J Clin Oncol 2000;19.
  11. 11. Randomized Phase III Trials of AIs vs. Tamoxifen as First-line Treatment of Postmenopausal MBC Anastrozole1 Anastrozole2 Letrozole3 Exemestane4No. patients 170 vs 182 340 vs 328 453 vs 454 182 vs 189ORR, % 21 vs 17 33 vs 33 32 vs 21* 46 vs 31*CBR, % 59 vs 46* 56 vs 56 50 vs 38* 66 vs 49*TTP or PFS, months 11 vs 6* 8 vs 8 9 vs 6* 10 vs 6*ER status unknown, % 11 vs 11 56 vs 54 34 vs 33 15 vs 11ORR = overall response rate; CBR = clinical benefit rate; TTP = time to progression; PFS = progression free survival; ER = estrogen receptor *Statistically significant difference 1. Nabholtz JM, et al. J Clin Oncol. 2000;18 2. Bonneterre J, et al. J Clin Oncol. 2000;18 3. Mouridsen H, et al. J Clin Oncol. 2003;21 4. Paridaens R, et al. J Clin Oncol. 2008;26
  12. 12. Hormonal Therapy in PostmenopausalMBC: Aromatase Inhibitors All three AIs showed higher RR and longer TTP compared to Tam in first line setting; no differences in long term OS (Mouridsen et al JCO 2003; Bonneterre et al Cancer 2001, Paridaens et al, ASCO 2004); All three AIs seem to be equally effective with slight differences in untoward effects (Rose et al ASCO 2002, Cameron et al , ASCO 2004, Mayordomo et al, ASCO 2006) The efficacy of AIs after Tam is comparable to the efficacy of Tam after AIs (Thurlimann et al, EJCancer 2003) Steroid inactivator exemestane is effective after failure to nonsteroidal AIs, nonsteroidal AIs are effective after failure to exemestane (Thurlimann et al, EJCancer 1997, Bertelli G, et al. Oncology. 2005)
  13. 13. FIRST: Fulvestrant 500 mg vs. Anastrozole as First-Line 1.0 Proportion of patients alive and progression-free 0.8 Fulvestrant 500 mg Anastrozole 1 mg 0.6 0.4 0.2 HR = 0.66 (95% CI: 0.47-0.92) P = .01 0.0 0 6 12 18 24 30 36 42 48 Time (months) Number of patients at risk: Fulvestrant 500 mg 102 74 65 52 45 34 20 6 0 Anastrozole 1 mg 103 69 55 39 30 21 8 2 0 CI = confidence interval; HR = hazard ratio; TTP = time to progressionRobertson JF, et al. Cancer Res. 2010;70: Abstract S1-3.
  14. 14. How to Overcome Resistance to ET ?  mTORC1 activates ER in a ligand-independent fashion1  Estradiol suppresses apoptosis induced by PI3K/mTOR blockade2  Hyperactivation of the PI3K/mTOR pathway is observed in endocrine- resistant breast cancer cells3  mTOR is a rational target to enhance the efficacy of hormonal therapy1. Bjornsti MA, et al. Nat Rev Cancer. 2004;4(5):335-348. 2. Crespo JL, et al. Microbiol Mol Biol Rev. 2002;66(4):579-591.3. Huang S, et al. Cancer Biol Ther. 2003;2(3):222-232. 4. Mita MM, et al. Clin Breast Cancer. 2003;4(2):126-137.5. Wullschleger S, et al. Cell. 2006;124(3):471-484. 6. Johnston SR. Clin Cancer Res. 2005;11(2 Pt 2):889S-899S.
  15. 15. TAMRAD: Tamoxifen +/- Everolimus as Second- Line After AIs Failure 1.0 0.9 Probability of survival 0.8 0.7 0.6 0.5 0.4 TAM TAM + RAD 0.3 0.2 Hazard Ratio (HR) = 0.32 (95% CI: 0.15-0.68) Exploratory log-rank: P = .0019 0.1 0.0 0 3 6 9 12 15 18 21 24 27 30 33 36 Months Patients at risk:TAM + RAD: n = 54 53 51 49 49 45 38 26 14 6 0 TAM: n = 57 55 53 50 44 38 30 22 9 4 0CI = confidence interval; HR = hazard ratio; RAD = RAD001; TAM = tamoxifenBachelot T, et al. Cancer Res. 2010;70: Abstract S1-6.
  16. 16. BOLERO-2: Exemestane +/- Everolimusin AI Refractory Disese N = 724 Everolimus 10 mg/day + PFS Exemestane 25 mg/dayPostmenopausal (N = 485) 2 OSER+ HER2- ABC ORR refractory to 1 Bone Markers letrozole or Placebo + Safety anastrozole Exemestane 25 mg/day PK (N = 239)  Stratification:  Sensitivity to prior hormonal therapy  Presence of visceral disease  No crossoverABC: advanced breast cancer, NSAI: non steroidal aromatase inhibitors, HER2-: human epidermal growth factor receptor 2 – negative;PFS: progression-free survival; PK: pharmacokineticsBaselga J, et al. Eur J Cancer Suppl. 2011;47(Suppl 2): Abstract: 9LBA.
  17. 17. BOLERO-2 Primary Endpoint: PFS Local Assessment HR = 0.43 (95% CI: 0.35–0.54) 100 Log rank P value = 1.4 x 10 -15 80 EVE + EXE: 6.9 months Probability of Event, % PBO + EXE: 2.8 months 60 40 20 Everolimus + Exemestane (E/N = 202/485) Placebo + Exemestane (E/N = 157/239) 0 0 6 12 18 24 30 36 42 48 54 60 66 72 78 Time, weeks No. of Patients Still at Risk: Everolimus 485 398 294 212 144 108 75 51 34 18 8 3 3 0 Placebo 239 177 109 70 36 26 16 14 9 4 3 1 0 0Baselga J, et al. Eur J Cancer Suppl. 2011;47(Suppl 2): Abstract: 9LBA.
  18. 18. Chemotherapy for MBCCombination Chemotherapy or Sequential Use ofMonotherapy? Most trials and meta-analysis compare single agent vs. combination and NOT sequential use of single agents vs. combination CT. The majority of trials show that combination CT yields higher RR, in some higher PFS, higher toxicity and no or quite small survival benefit.
  19. 19. Chemotherpy Agents = Survival Gains Pooled analysis of 6 consecutive trials of first-line CT in MBC: - Clear evidence of an increase in OS during the past 20 years, starting with the inclusion of paclitaxel 100 90 80 1998-2001 70 Median OSProbability % 1995-1997 60 1992-1994 - 18.0 mos, in 1983-1986 50 1987-1989 - 17.2 mos, in 1987-1989 1983-1986 40 - 19.2 mos, in 1992-1994 30 - 26.1 mos, in 1995-1997 - 23.6 mos, in 1998-2001 cohorts 20 (P for heterogeneity .0001) 10 0 0 1 2 3 4 5 6 7 8 Years CT, chemotherapy; OS, overall survival Gennari A, et al. Cancer. 2005;104(8):1742-1750.
  20. 20. Randomized Studies with Crossover Following in the Monotherapy Arm Time to Overall Author Comparison Number of Response Rate Progression Survival Year (x number of cycles) patients (%) (months) (months) Alba A x 3 Doc x 3 144 61 10.5 22.3 2004 A + Doc x 6 51 9.2 21.8 Beslija Doc  X 100 40 7.7 19.0 2006 Doc + X 68* 9.3* 22.0* Conte E x 4  Pac x 4 202 58 10.8‡ 26.0 2004 E + Pac x 8 58 11.0‡ 20.0 Koroleva Doc x 4  A x 4 193 56 6.9 13.8 2001 A + Doc x 8 49 6.7 11.9 A + Doc║ x 8 59 8.3 14.5 Sjöstrom Doc 238 42* 6.3* 10.4 1999 MF 21 3.0 11.1 Sledge A 739 36 5.8¶ 18.9 2003 Pac 34 6.0¶ 22.2 A + Pac 47* 8.0*¶ 22.0 Soto X  Pac or Doc 368 45 8.4‡ 31.5 2006 X + Pac 64* 6.7‡ 33.1 X + Doc 75* 8.1‡ 28.5 Tomova Doc x 4 G x 4 100 28 6.7 15.9 2008 Doc + G x 8 31 7.0 15.5 *Denotes statistically significant result with P≤.05Cardoso F, et al. J Natl Cancer Inst. 2009;101(17):1174-1181
  21. 21. COMBINATION SEQUENTIAL SINGLE AGENTS >RR Similar survival ! <ToxicityFaster symptom/disease control Better overall QoL Better management of resources
  22. 22. New Cytotoxic Agents New cytotoxic agents  Targeting microtubules: Eribulin, Epothilones “Old” agents in new formulations  Capecitabine (considered standard in A&T pretreated pts)  Liposomal anthracyclines  New formulations of anti-microtubules: albumin bound, nab- paclitaxel “Old” agents in new indications  Platinum & Alkylating agents for TN
  23. 23. EMBRACE: A Phase III Study of Eribulin inHeavily Pre-treated pts: Overall Survival (ITT) 1.0 1-Year Survival Eribulin (n = 508) 53.9% 0.8 TPC (n = 254) 43.7% Survival Probability Eribulin median 13.12 months 0.6 TPC HR* 0.81 (95% CI: 0.66, 0.99) 0.4 median 10.65 months P value† = 0.041 0.2 2.47 months 0.0 0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 Overall Survival, monthsTwelves C, et al. J Clin Oncol. 2010;28(15s): Abstract CRA1004.
  24. 24. What is the optimal duration of chemotherapy ?
  25. 25. U1 Results: Progression Free Survival Optimal Duration of Study Longer better Shorter better %Weight HR 95%CI Coates 1987 13 0.56 0.44-0.71 Chemotherapy? Harris 1990 Muss 1991 2 3 1.18 0.26 0.65-2.15 0.16-0.43 Ejlertsen 1993 28 0.71 0.61-0.83 Gregory 1997 10 0.70 0.53-0.92 Falkson 1998 5 0.46 0.31-0.68 Bastit 2000 11 0.65 0.50-0.84 Nooij 2003 8 0.67 0.50-0.90 Gennari 2006 6 1.01 0.71-1.43 Majordomo 2009 8 0.77 0.57-1.05 Alba 2010 6 0.53 0.37-0.76 Overall 100 0.64 0.66 0.55-0.76 0.60-0.72U1 0.10 1.00 10.00 Results: Overall Survival Test for heterogeneity, p=0.001 Test for treatment effect, p<0.001 Study Longer better Shorter better %Weight HR 95%CI Coates 1987 13 0.79 0.62-1.01 Harris 1990 Muss 1991 2 5 1.06 1.11 0.57-1.97 0.74-1.67  Longer CT duration: Ejlertsen 1993 Gregory 1997 17 5 0.78 0.81 0.63-0.97 0.54-1.21  36% reduction in the risk of Falkson 1998 8 0.94 0.69-1.28 progression (HR 0.64; 95% Bastit 2000 Nooij 2003 18 17 0.96 1.03 0.78-1.18 0.83-1.27 CI 0.55 – 0.76) Gennari 2006 Majordomo 2009 4 7 1.12 0.94 0.73-1.72 0.67-1.32  9% reduction in the risk of Alba 2010 5 0.86 0.58-1.27 death (HR 0.91; 95% CI 0.84- Overall 0.10 1.00 10.00 100 0.91 0.84-0.99 0.99) Test for heterogeneity, p=0.69 Test for treatment effect, p=0.044 25 Gennari et al, ESMO 2010
  26. 26. Targeted Therapies in MBC HER2-directed therapy (considered standard in HER2+ disease) PARP inhibitors Antiangiogenic agents
  27. 27. Anti-HER2 Therapy in Combination with Chemotherapy in HER2-Positive MBC TTP OS Trial Treatment ORR (%) (months) (months)Slamon et al.1; Trastuzumab + 7.1 vs. 25.1 vs. 49 vs. 17*Smith et al. 2 paclitaxel vs. paclitaxel 3.0* 18.0* Trastuzumab + 11.7 vs. 31.2 vs.Marty et al.3 61 vs. 34* 6.1* 22.7* docetaxel vs. docetaxelDi Leo et al. 4 Lapatinib + paclitaxel 8.5 vs. 24.0 vs.(ErbB2+ 63 vs. 38* vs. paclitaxel 5.8* 19.8*patients only) Lapatinib + paclitaxel 9.7 vs. 27.8Guan et al. 5 69 vs. 50* 6.5* vs.20.5* vs. Paclitaxel *= statistically significant1. Slamon et al. N Engl J Med 2001;344, 2. Smith et al. Anticancer Drugs 2001;12 Suppl 4:S3–10, 3. Marty et al. J Clin Oncol 2005;23, 4. Di Leo et al. Clin Oncol 2008;26, 5. Guan et al. 33rd SABCS 2010; Abstract P3-14-24
  28. 28. First-line Treatment with Trastuzumab + Docetaxel or Vinorelbine in ErbB2+ MBC: HERNATA StudyAnderssen M, et al. J Clin Oncol 2011;29
  29. 29. Anti-HER2 Therapy in Combination withEndocrine Therapy in ER+/HER2+ MBC  Anastrozole + Trastuzumab (TANDEM)1  CB 28 v 43%; PFS 2.4 v 4.8 months   Letrozole + Lapatinib (EGF30008)2  CB 29 v 48%; PFS 3.0 v 8.2 months1. Kaufman, et al. J Clin Oncol 27 2009, 2. Johnston, et al. J Clin Oncol 27 2009,
  30. 30. TANDEM: Evaluation of Anastrozole +/- Trastuzumab in HER2+/HR+ MBC 100 A A+H Outcome P Value (n = 104) (n = 103) Progression-Free 80 Events, n 99 87 Survival (%) 60 Median PFS, mos 2.4 (2.0-4.6) 4.8 (3.7-7.0) .0016 (95% CI) 40 20 0 0 5 10 15 20 25 30 35 40 45 50 55 60 2.4 months Months A+H n = 103 48 31 17 14 13 11 9 4 1 1 0 0 A n = 104 36 22 9 5 4 2 1 0 0 0 0 0Kaufman, et al. J Clin Oncol 2009.
  31. 31. TANDEM: Evaluation of Anastrozole +/- Trastuzumab in HER2+/HR+ MBC Anastrozole N=207 Anastrozole +Median age 55 years TrastuzumabVisceral disease 1/3 Prior chemo 1/2 Cross-over 70% 6,8% Response rate 20,3% p 0.0016 2,4m Median PFS. 4,8m 23,9m Median O.S. 28,5m 32,1m Median O.S. 41,9m if no liver mets p 0.03Trastuzumb added to anastrozole  RR, PFS (and possibly OS if no liver mets) IMPORTANCE OF STARTING BIOLOGICAL AGENT SOONMackey, et al. SABC 06;abst.03. Adapted from M. Piccart
  32. 32. Current Evidence Based Options of Anti-HER2 Treatment Beyond TrastuzumabProgression (Phase III trials) Continuing trastuzumab (GBG 26 / BIG 3-05 study) Lapatinib + capecitabine (EGF100151 study) Lapatinib + trastuzumab (EGF104966 study)
  33. 33. Comparison of Three Prospective Phase IIITrials on Anti-HER2 Treatment BeyondTrastuzumab Progression GBG-26a EGF100151b EGF104900a (n=156) (n=399) (n=296)Regimen XH X XL X LH LORR, % 48 27 32 17 10 7TTPc HR 0.69 (p=0.03) 0.72 (p=0.01) 0.73 (p=0.01) Median, 8.2 5.6 5.5 4.2 2.8 1.9 monthsOS HR 0.76 (p=0.26) 0.78 (p=0.18) 0.74 (p=0.02) Median, 25.5 20.4 15.6 15.3 14.0 9.5 months aVon Minckwitz et al 2008; O’Shaughnessy et al 2008; bInvestigator Assessment, US Lapatinib Prescribing Information & Cameron et al 2008;
  34. 34. New HER2-directed Agents Pertuzumab (first-in-class ErbB dimerisation inhibitor)  Phase 2 trials completed, undergoing phase 3 in combination with trastuzumab (CLEOPATRA trial) Neratinib (oral, pan-ErbB TKI)  Phase 2 trials in monotherapy and in combination with paclitaxel or vinorelbine completed, undergoing phase III combination trial with paclitaxel (NEFERTT trial) Afatinib (oral irreversible ErbB1 and 2 inhibitor)  Phase III trial in combination with vinorelbine (Lux-Breast1) Trastuzumab - DM1 (HER2-targeted antibody-drug conjugate)  In phase2 trial comperable efficacy with better toxicity profile compared to trastuzumab and docetaxel  Ongoing phase 3 trials
  35. 35. TDM4450g : Progression-Free Survival Median Hazard Log-rank PFS, mos ratio 95% CI P value Trastuzumab 1.0 + docetaxel (n=70) 9.2 0.364– 0.594 .0353 Proportion Progression-Free T-DM1 (n=67) 14.2 0.968 0.8 0.6 0.4 0.2 0.0 0 2 4 6 8 10 12 14 16 18 20 Time, monthsNumber of patients at riskT+D 70 66 63 53 43 27 12 4 2 2 0T-DM1 67 60 51 46 42 35 22 15 6 3 0Hazard ratio and log-rank P value were from stratified analysis.Hurvitz S, et al. Eur J Cancer Suppl. 2011;47(Suppl 2): Abstract 5001.
  36. 36. Biological agents for HER-2 negative disease
  37. 37. Bevacizumab: First-Line MBC Meta Analysis E2100 Paclitaxel RANDOMIZE Chemo + OptionalPreviously Treat Second-line AVADO No BVUntreated Chemo + BV Docetaxel until (AVADO and MBC Chemo + PD RIBBON-1 BV only) RIBBON-1 Capecitabine, Taxane, or Anthracycline O’Shaugnessy J, et al. J Clin Oncol. 2010;28(15S): Abstract 1005.
  38. 38. Bevacizumab in MBC RIBBON-1: E21001 AVADO2 Capecitabine3 RIBBON-1: A/T3Placebo (Pl) controlled No Yes Yes Yes q 3 wk WeeklyChemotherapy q 3 wk docetaxel (D) Capecitabine (C) docetaxel/nabPAC/FA paclitaxel (P) C/EC/FEC 10 mg/kg 7.5 or 15 mg/kg 15 mg/kg 15 mg/kgDose of bevacizumab (B) q 2 wk q 3 wk q 3 wk q 3 wk P P+B D+PI D+B C+PI C+B A/T+PI A/T+BORR 25% 49% 49% 55%/63% 24% 35% 38% 51%PFS, months 5.9 11.8 80 8.7/8.8 5.7 8.6 8.0 9.2 0.79 (7.5 mg) 0.60 P = .0318 0.69 0.64HR P<.0001 0.72 (15 mg) P = .0002 P<.0001 P = .0099OS, months 25.2 26.7 NR NR 21.2 29 23.8 25.2 0.88 0.92 (7.5 mg) 0.85 1.03HR P = .16 0.86 (15 mg) P = .27 P = .83 Meta-Analysis (O’Shaughnessy et al ASCO 2010) PFS: 2.5 months, OS: 0.3 months1.Miller K, et al. N Eng J Med. 2007;357(26), 2. Miles D, et al. J Clin Oncol. 2008;26:(May 20 Suppl): AbstractLBA1011, 3. Robert NJ, et al. J Clin Oncol. 2009;27(15S): Abstract 1005.
  39. 39. Multi-center, Randomized Open-label Phase III RegistrationNTrial of Iniparib in mTNBC = 519 Patient Population:  mTNBC Gem/Carbo (GC) Crossover allowed  0–2 prior chemo for (N= 258) metastatic TNBC to GCI following Gemcitabine 1000 mg/m2 IV d 1, 8 Disease Progression*  Stable CNS metastases Carboplatin AUC2 IV d 1, 8 (central review) allowed 21-day cycles Stratification: R  No prior chemo vs 1–2 Gem/Carbo + Iniparib (GCI) prior chemo for mTNBC (N= 261) Gemcitabine - 1000 mg/m2 IV d 1, 8 Carboplatin - AUC2 IV d 1, 8 Endpoints: Iniparib - 5.6 mg/kg IV d 1,4,8,11  Primary: OS, PFS 21-day cycles  Secondary: ORR, safety/tolerability96% (n=152) of progressing patients crossed over to GCI at time of primary analysisO’Shaughnessy et al, ASCO 2011
  40. 40. Efficacy Endpoints – ITT Population GC* GCI GC GCI PFS OS (N=258) (N=261) (N=258) (N=261) Median PFS, mos 4.1 5.1 Median OS, mos 11.1 11.8 (95% CI) (3.1, 4.6) (4.2, 5.8) (95% CI) (9.2, 12.1) (10.6, 12.9) HR (95% CI) 0.79 (0.65, 0.98) HR (95% CI) 0.88 (0.69, 1.12) 1.0 p-value 0.027 1.0 p-value 0.28 Probability of Progression Free Survival 0.9 0.9 0.8 0.8 Probability of Survival 0.7 Pre-specified alpha = 0.01 0.7 Pre-specified alpha = 0.04 0.6 0.6 0.5 0.5 0.4 0.4 0.3 0.3 0.2 0.2 0.1 0.1 0 0 0 2 4 6 8 10 12 14 16 0 2 4 6 8 10 12 14 16 Months Since Study Entry MonthsNo. at risk No. at riskGC 258 171 116 63 38 18 6 1 0 GC 258 239 214 181 151 99 38 11 0GCI 261 187 138 83 53 11 2 0 0 GCI 261 248 230 204 169 111 52 15 0O’Shaughnessy et al, ASCO 2011
  41. 41. Potential Solutions to Improve MBCOutcome New treatments New strategies with “old” treatments More pts in clinical trials Less than 5-10% of cancer patients participate in clinical trials in the western countries!! Biomarkers (predictive, pharmacogenetics, pharmacogenomics…) International RECOMMENDATIONS (that are followed!) (implementation of recommendations such as St Gallen increased survival EBC)
  42. 42. The “St Gallen” of MBC PLEASE JOIN US!!

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