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SABCS 2012

SABCS 2012. Guy Jerusalem, MD, PhD. SABCS 2012: Clinical studies in HER2 negative disease. Hunderds of oral and poster presentations to be covered (endocrine therapy , chemo , targeted therapy )

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SABCS 2012

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  1. SABCS 2012 Guy Jerusalem, MD, PhD

  2. SABCS 2012: Clinicalstudies in HER2 negativedisease • Hunderds of oral and poster presentations to becovered (endocrine therapy, chemo, targetedtherapy) • Selectioncriteria for mypresentation: phase 3 studiescontributing to respond to important clinical questions

  3. Impact of the ATLAS trial? • Premenopausal patients (10% of study population) The new standard? • Postmenopausal patients Use of AI

  4. My opinion • Postmenopausal patients • I consider 5 years of TAM as an option in high risk patients after 5 years of AI (discussion with the patient indicating of course thatthisis not an evidence-basedapproach)

  5. Final analysis of overall survival for the Phase III CONFIRM trial: fulvestrant 500 mg versus 250 mg Angelo Di Leo, Guy Jerusalem, Lubos Petruzelka, Roberto Torres, Igor N. Bondarenko, Rustem Khasanov, Didier Verhoeven, José L. Pedrini, Iva Smirnova, Mikhail R. Lichinitser, Kelly Pendergrass, Sally Garnett, Yuri Rukazenkov, Miguel Martin, on behalf of the CONFIRM investigators San Antonio Breast Cancer Symposium – Cancer Therapy and Research Center at UT Health Science Center – December 4-8, 2012 This presentation is the intellectual property of the author/presenter. Contact them at adileo@usl4.toscana.it for permission to reprint and/or distribute

  6. San Antonio Breast Cancer Symposium – Cancer Therapy and Research Center at UT Health Science Center – December 4-8, 2012 Trial design and main eligibility criteria Fulvestrant 250 mg (1 injection i.m.) + placebo (1 injection i.m.) days 0, 14 (2 placebo injections), 28, and every 28 days thereafter • Post-menopausal • Advanced disease • ER+ Fulvestrant 500 mg (2 injections 250 mg i.m.) days 0, 14, 28, and every 28 days thereafter Allowed prior hormonotherapy (HT) Relapsing pts. “de novo” advanced pts. X X X 1st line HT X start adjuvantHT 5 yrs. 12 mos. gap 1st line HT

  7. San Antonio Breast Cancer Symposium – Cancer Therapy and Research Center at UT Health Science Center – December 4-8, 2012 Primary endpoint: progression-free survival 1.0 Proportion of patients progression-free Fulvestrant 500 mgFulvestrant 250 mg 0.8 HR = 0.80; 95% CI: 0.68, 0.94;p=0.006 0.6 Median PFS (months) Fulvestrant 500 mg 6.5 Fulvestrant 250 mg 5.5 0.4 0.2 0.0 40 0 4 8 12 16 20 24 28 32 36 44 48 Time (months) Patients at risk:500 mg250 mg 362374 216199 163144 11385 9060 5435 3725 1912 124 73 31 21 00 CI, confidence interval; HR, hazard ratio;PFS, progression-free survival Di Leo A et al. J Clin Oncol 2010; 28: 4594-4600 This presentation is the intellectual property of the author/presenter. Contact them at adileo@usl4.toscana.it for permission to reprint and/or distribute

  8. San Antonio Breast Cancer Symposium – Cancer Therapy and Research Center at UT Health Science Center – December 4-8, 2012 Secondary endpoint: overall survival (first analysis at 50% maturity – full analysis set) 1.0 Proportion of patients alive Fulvestrant 500 mgFulvestrant 250 mg 0.8 HR = 0.84; 95% CI: 0.69, 1.03;p=0.091 0.6 0.4 Median time to death (months) Fulvestrant 500 mg 25.1 Fulvestrant 250 mg 22.8 0.2 0.0 0 4 8 12 16 20 24 28 32 36 40 44 48 Time (months) Patients at risk:500 mg250 mg 362374 330338 285299 251260 223222 165157 116107 7461 4634 2918 1610 62 00 Di Leo A et al. J Clin Oncol 2010; 28: 4594-4600 This presentation is the intellectual property of the author/presenter. Contact them at adileo@usl4.toscana.it for permission to reprint and/or distribute

  9. San Antonio Breast Cancer Symposium – Cancer Therapy and Research Center at UT Health Science Center – December 4-8, 2012 Overall survival (final analysis at 75% maturity – full analysis set) Proportion of patients alive 1.0 Fulvestrant 500 mg 0.9 Fulvestrant 250 mg 0.8 0.7 0.6 0.5 aNominal value, cannot be claimed as statistically significant 0.4 0.3 Median time to death (months) Fulvestrant 500 mg 26.4 Fulvestrant 250 mg 22.3 0.2 0.1 0 0 4 8 12 16 20 24 28 32 36 40 44 48 52 56 60 64 68 72 76 80 Time (months) Patients at risk: 250 mg 374 338 299 261 223 191 164 137 112 96 87 74 64 48 37 22 14 8 3 2 0 500 mg 362 333 288 254 227 202 178 163 141 123 114 98 81 64 47 30 26 15 8 1 0 This presentation is the intellectual property of the author/presenter. Contact them at adileo@usl4.toscana.it for permission to reprint and/or distribute

  10. First subsequent therapies San Antonio Breast Cancer Symposium – Cancer Therapy and Research Center at UT Health Science Center – December 4-8, 2012 * 8 out of 374 patients (2.1%) shifted from fulvestrant 250 mg to fulvestrant 500 mg either at the time of PD to 250 mg (4 pts.) or in absence of PD (4 pts.)

  11. Conclusion and clinical impact • This 4-month OS benefitisclinically relevant althoughsurprising (only 1-month PFS benefit) • A better endocrine therapy in first or second line ER positive breast cancer canimprovesurvival (TAMRAD, trend in BOLERO 2 – mature OS resultsexpected in 2013) • 500 mg isalreadyapproved as the new standard dose and isused in our routine practice

  12. Conclusion and clinical impact • LEA is a negative trial although a smallbenefit (<31% reduction in PFS withbevacizumab) cannotberuled out by thisstudy; bev has no impact on OS • More promisingcombinedtreatments (endocrine therapy and targetedtherapy) are underevaluation

  13. Conclusion and clinical impact • First randomized phase 3 trial specifically in early TNBC; 3 year IDFS betterthanexpected. • The BEATRICE trial demonstrated no statisticallysignificantimprovement in invasive DFS • Results are consistent withdisappointing data observed in the adjuvant treatment of early colon cancer

  14. CALGB 9741 / Intergroup Trial 2 x 2 Factorial Design In Node Positive Disease q 2 wk (w/G-CSF) q 3 wk 33 weeks 22 weeks 14 weeks 21 weeks doxorubicin 60 mg/m2 cyclophosphamide 600 mg/m2 paclitaxel 175 mg/m2 over 3 hours Radiation therapy and tamoxifen followed as appropriate Citron, et al. JCO 2003, 21:1431-1439

  15. DFS by Dose Density (Q2 vs Q3) 11/30/2005 q2wk q3wk Disease-free survival Q2 n = 988 Events = 230 p = 0.012 Q3 n = 984 Events = 278

  16. OS by Dose Density (Q2 vs Q3) 11/30/2005 q2wk q3wk Overall survival Q2 n = 988 Events = 168 p = 0.049 Q3 n = 984 Events = 202

  17. Conclusion and myinterpretation • TACT trial : unable to confirm the results of the Citron trial • Dose-dense epirubicine (4 cycles) does not improve TTR; actualdelivered dose-intensitywas OK • Explanation ??? • Role of taxanes? • Lenght of follow-up?

  18. Conclusion and myinterpretation • Shouldwe stop using dose-dense chemo? • The Citron trial is not the onlysuccess story of dose-dense chemotherapy (dose-dense adriamycine/cyclophosphamide in NHL, dose-dense paclitaxel in ovarian cancer) • Good rationale (Norton-Simon hypothesis) for using dose-dense chemotherapy in highlyproliferativetumors

  19. Conclusion and myinterpretation • Interestingresults; suggestthatwecanstillimproveour standard chemoregimens • All parts of thisregimen are differentfromcurrent standards… • Dose-density? Dose-intensity? Early use of dose-dense paclitaxel? • I will not use thisregimen…

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