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SHARE Presentation: New Developments in the Medical Treatment of Breast Cancer 2015

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Dr. Cliff Hudis on the latest information on new breast cancer treatments. Dr. Hudis is Chief of Breast Cancer Medicine Service at Memorial Sloan-Kettering Cancer Center.

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SHARE Presentation: New Developments in the Medical Treatment of Breast Cancer 2015

  1. 1. Newest treatments for all stages of breast cancer including hormonal treatments and developments in HER2 positive breast cancer Clifford Hudis, M.D. Chief, Breast Medicine Service, MSKCC Professor of Medicine, Weill Cornell Medical College Immediate Past President, American Society of Clinical Oncology
  2. 2. Cancer in general 300,000,000 Americans • 560,000 cancer deaths (2/1000/year = 0.2%) – lung cancer, (160,000) – colorectal (53,000) – breast (41,000) – pancreas (33,000) – prostate (27,000). • Mostly age 55 and older. • Deaths in childhood (0 and 14) are rare (1,500)
  3. 3. Epidemiology 200,000 new cases Approx 40,000 deaths Lifetime risk: Approximately 1:8 will develop breast cancer (cumulative risk) American Cancer Society. Detailed Guide: Breast Cancer: What are the Key Statistics for Breast Cancer? Available at: http://www.cancer.org. Accessed Sept. 14, 2009.
  4. 4. Breast Pathology Breast Carcinoma In situ Infiltrating Carcinoma Ductal Carcinoma In Situ Lobular Carcinoma In Situ Infiltrating Ductal, nos (70 - 80%) Invasive Lobular (5 - 10%) Others From: DeVita VT et al. Cancer: Principles and Practice of Oncology. 7th Ed. Philadelphia, Pennsylvania: Lippincott Williams & Wilkins; 2005:1415-1477.
  5. 5. Risk Factors for Breast Cancer • Gender • Age • Race • Diet high in fat • Early onset of menses and late menopause • Late or no pregnancies • Family history (BRCA1, BRCA2) • Dense breast tissue • Alcohol consumption • Hormone supplementation American Cancer Society. Breast Cancer Facts and Figures 2005-2006.
  6. 6. Sub-classification of BC: Three Diseases ER and/or PR (+) ER and PR (-) HER2 (+) “Triple Positive” “HER2 positive” HER2 normal “Hormone sensitive” “TNBC”
  7. 7. Sub-classification of BC: Three Diseases ER and/or PR (+) ER and PR (-) HER2 (+) “Triple Positive” “HER2 positive” HER2 normal “Hormone sensitive” “TNBC”
  8. 8. Sub-classification of BC: Three Diseases ER and/or PR (+) ER and PR (-) HER2 (+) “Triple Positive” “HER2 positive” HER2 normal “Hormone sensitive” “TNBC”
  9. 9. Sub-classification of BC: Three Diseases ER and/or PR (+) ER and PR (-) HER2 (+) “Triple Positive” “HER2 positive” HER2 normal “Hormone sensitive” “TNBC”
  10. 10. How Long Should Post-Operative Hormone Therapy Last?
  11. 11. Survival after a Diagnosis of Breast Cancer. Foulkes WD et al. N Engl J Med 2010;363:1938-1948. Breast Cancer Recurrences Occur Late
  12. 12. 13 SUPPORTING TRIALS • ATAC – updated at SABCS 2004 • BIG FEMTA • TEAM (not yet reported) SUPPORTING TRIALS • no reported trials • BIG FEMTA SUPPORTING TRIALS • IES – updated at SABCS 2004 • ITA • ARNO/ABCSG - reported at SABCS 2004 Adjuvant AI Hormonal Therapy Trial Designs * * Note that some patients from the original newly diagnosed population are lost due to recurrence or adverse events prior to randomization DIRECT COMPARISON SWITCHING * SEQUENCING EXTENDED ADJUVANT SUPPORTING TRIALS • MA-17 – updated ASCO 2004
  13. 13. MA.17 Letrozole in the Extended Adjuvant Setting Improved DFS with 5 yrs of Letrozole After 5 yrs of Tamoxifen Goss. PE. Breast Cancer Res Treat. 2007 October; 105(Suppl 1): 45–53. Epub 2007 Oct 3.
  14. 14. B33: (Stopped Early) Exemestane versus placebo (intent-to-treat, eligible patients, w/follow-up): DFS Mamounas E P et al. JCO 2008;26:1965-1971 ©2008 by American Society of Clinical Oncology
  15. 15. NSABP B14: Patients Re-randomized After 5 years of Tamoxifen to Either Placebo or Prolonged Tamoxifen (10 vs 5 years) Fisher B et al. JNCI J Natl Cancer Inst 2001;93:684-690 n=117 2
  16. 16. Objectives of ATLAS & aTTom • Randomise at least 20,000 women between 10 and 5 years of tamoxifen (to detect reliably, or refute reliably, a 2-3% improvement in survival) • Follow-up randomised women for at least 15 years (because 10 or more years is needed to see full benefits from longer tamoxifen*) *Peto R, Five Years of Tamoxifen—or More? JNCI 1996
  17. 17. ECOG, Scottish & NSABP B-14 1,588 ATLAS 11,646 aTTom 6,953 ALL TRIALS 20,187 20,187 women with ER-positive or ER- unknown disease randomised in 5 trials of 10 vs 5 years of tamoxifen: ATLAS, Lancet 2013; 381: 805–16 aTTom: Proc ASCO 2013
  18. 18. 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 ATLAS. Contact ATLAS@CTSU.ox.ac.uk for permission to reproduce or distribute. ATLAS: 6846 women, ER+, 10 vs 5 years tamoxifen RECURRENCE BREAST CANCER MORTALITY
  19. 19. aTTom: 10 vs 5 years of tamoxifen: Recurrence by treatment ASCO 2013 580 vs 672 recurrences RR=0.85 (95%CI 0.76-0.95) p=0.003 Presented ASCO 2013
  20. 20. Concepts to consider •Chronic, relatively steady recurrence risk •Relatively low rate of mortality •Time Dependent Effects: Duration of effect on the rate Development of resistance Development of intolerance •Long term toxicities •Absolute benefit to the individual •DRUG-SPECIFIC or DURATION (of any rx)?
  21. 21. ASCO’s CancerLinQ: Big Data Sledge GW, Hudis CA, Swain SM, et al: ASCO's approach to a learning health care system in oncology. J Oncol Pract 9:145–148, 2013
  22. 22. ASCO’s CancerLinQ prototype • Development began in June of 2012. • Completed in eight months. • Included more than 170,000 de-identified patient records. • Demonstrated that the full CancerLinQ system could be a reality. Kolacevski A, Mann JT, Hauser R, et al: Using Big Data to Track Trends in Medical Practice. Journal of Oncology Practice 11:JOP.2014.001541–70, 2014
  23. 23. Tamoxifen Duration & Survival In CLQ Pilot Accessed 16 March 2015 at: http://bcove.me/evt9lbbp
  24. 24. Do Young Women Need To Be Made Menopausal?
  25. 25. Hormone Therapy Was The First Targeted Therapy 1896 GT Beatson - Oophorectomy in premenopausal women 1944 A Haddow - Synthetic estrogen (stilbestrol) as treatment of breast cancer 1952 C Huggins - Adrenalectomy (1966 Wins Nobel Prize for development of endocrine therapy in prostate cancer) 1958 E Jensen - Characterization of the estrogen receptor (ER)
  26. 26. TEXT and SOFT Designs Presented by: Olivia Pagani, MD ASCO 2014 R A N D O M I Z E Tamoxifen+OFS x 5y Exemestane+OFS x 5y R A N D O M I Z E Tamoxifen x 5y Tamoxifen+OFS x 5y Exemestane+OFS x 5y Tamoxifen+OFS x 5y Exemestane+OFS x 5y Joint Analysis (N=4690) • Premenopausal • ≤12 wks after surgery • No chemo OR • Remain premenopausal ≤ 8 mos after chemo • Premenopausal • ≤12 wks after surgery • Planned OFS • No planned chemo OR planned chemo SUPPRESSION OF OVARIAN FUNCTION TRIAL (N=3066) TAMOXIFEN AND EXEMESTANE TRIAL (N=2672) OFS=ovarian function suppression Enrolled: Nov03-Apr11 Median follow-up 5.7 years TEXT SOFT
  27. 27. Exemestane+OFS Reduced Recurrence • 4% absolute improvement in 5-yr freedom from breast cancer for exemestane+OFS • No significant difference in overall survival Presented by: Olivia Pagani, MD ASCO 2014
  28. 28. SOFT: Tam vs OS/Tam Francis P et al, NEJM DOI: 10.1056/NEJMoa1412379
  29. 29. HER Family Receptors Hudis C. N Engl J Med 2007;357:39-51
  30. 30. H Trastuzumab Doxorubicin Cyclophosphamide Paclitaxel Docetaxel Carboplatin Adjuvant Trastuzumab NSABP B-31 NCCTG 9831 BCIRG 006 H… x 1 year H… x 2 years No therapy Standard ChemoRx HERA FinHer PACS 04 H…x9 H…x9 H…x 52 No therapy Epirubicin Vinorelbine Fluorouracil H…x 52 H…x 52 H…x 52 H…x 52 H…x 52
  31. 31. Can We Accelerate? Is Change In pCR A Reliable Surrogate?
  32. 32. Neoadjuvant Trastuzumab + Pertuzumab Regimen Duration pCR P value NEOSPHERE (N=417) DH 29% DP 12 w 24% DHP 45.8% 0.0141 HP 16.8% TRYPHAENA (N=225) FECHP → DHP 61.6% FEC → DHP 24 w 57.3% DCbHP 66.2% E=epirubicin; C=cyclophosphamide; F=fluorouracil; D=docetaxel; Cb=carboplatin; H=trastuzumab; P=pertuzumab
  33. 33. NeoAdjuvant Approval: Pertuzumab Unique circumstances? -Significant improvement in pCR -Significant increase in OS (MBC) - Completed, fully powered adjuvant trial -Significant safety experience (MBC & ongoing) Implications? Is Accelerated Approval a public health benefit? Why? - Because increased pCR is a leading indicator for OS? - If so, why not give a full year of pertuzumab? (Since that is what APHINITY tests.)
  34. 34. Neoadjuvant Lapatinib Trials Regimen Duration pCR P value NSABP B-41 (N=529) AC → PH 28 w 52.5% AC → PL 53.2% 0.99 AC → PHL 62% 0.095 NEOALTTO (N=455) *PH 18 w 29.5% *PL 24.7% 0.34 *PHL 51.3% 0.0001 CHERLOB (N=121) PH → FEC/H 24 w 25%^ PL → FEC/L 26.3%^ NR PHL → FEC/HL 46.7%^ 0.019 GEPAR-QUINTO (620) EC/H → DH 24 w 30.3%# EC/L → DL 22.7%# 0.04 A=doxorubicin; E=epirubicin; C=cyclophosphamide; F=fluorouracil; P=paclitaxel q w ; D=docetaxel q 3 w; H=trastuuzmab; L=lapatinib; *In NEOALTTO, 6 w of H or L or HL preceding P; ^ pCR (no invasive tumor breast and nodes); # pCR (no invasive or in situ tumor in breast and nodes; NR=not reported
  35. 35. •Patients with ER or PgR-positive tumors receive endocrine therapy selected accordingly to menopausal status; endocrine therapy will be started after the end of chemotherapy, will be administered concurrently with targeted therapies and will be planned for at least 5 years • Radiotherapy if indicated ALLTO 3-weekly Trastuzumab for 52 weeks Lapatinib for 52 weeks Weekly Trastuzumab (12 weeks) Lapatinib + 3-weekly Trastuzumab for 52 weeksWashout (6 weeks) Lapatinib (34 weeks) Anti-HER2 therapy can overlap chemotherapy
  36. 36. San Antonio Breast Cancer Symposium- Cancer Therapy and Research Center at UT Health Science Center- December 10-14, 2013 Study Design (APT Trial) This presentation is the intellectual property of the author/presenter. Contact them at stolaney@partners.org for permission to reprint and or distribute HER2+ ER+ or ER- Node Negative < 3 cm Enroll T P T P T P T P T P T P T P T P T P T P T P T P PACLITAXEL 80 mg/m2 + TRASTUZUMAB 2 mg/kg x 12 TT T T T T T T T T T T T FOLLOWED BY 13 EVERY 3 WEEK DOSES OF TRASTUZUMAB (6 mg/kg)* Planned N=400 *Dosing could alternatively be 2 mg/kg IV weekly for 40 weeks ** Radiation and hormonal therapy was initiated after completion of paclitaxel
  37. 37. San Antonio Breast Cancer Symposium- Cancer Therapy and Research Center at UT Health Science Center- December 10-14, 2013 Time (Months) Disease-FreeSurvival(Probability) 0 12 24 36 48 60 0.00.20.40.60.81.0 0 12 24 36 48 60 0.00.20.40.60.81.0 All patients Number at risk 406 390 382 307 126 27 Disease-Free Survival This presentation is the intellectual property of the author/presenter. Contact them at stolaney@partners.org for permission to reprint and or distribute 3-year DFS 95% Conf. Interval 98.7% 97.6% to 99.8% Poisson p-value: <0.0001
  38. 38. San Antonio Breast Cancer Symposium- Cancer Therapy and Research Center at UT Health Science Center- December 10-14, 2013 Change Is Happening (Personalization Is Possible) Anatomy (risk) drives treatment (1990) Biology (responsiveness) drives treatment (2014)
  39. 39. US Health Spending at 17.7% of GDP is ~50% Greater than Others (and Still Rising) Projected US Health Spending 2020 → 20% GDP Kehhan SP, Cuckler GI, Sisko AM, Madison AJ, Smith SD, Lizonito JM, Poisal JA and olfe CJ. National Health Expenditure Projections: Modest Annual Growth Until Coverage Expands And Economic Growth Accelerates. Health Affairs. 2012 Jul;31(7):1600-12.
  40. 40. Higher Spending Does Not Increase Life Expectancy Health Care Expenditures and Life Expectancy (2005) Fuchs VR, Milstein A. N Engl J Med 2011;364:1985-19
  41. 41. Projected family health insurance premium costs and average household income HouseholdIncome YearAnnals of Family Medicine: 2012: 10: 156-162 Patients are Bearing More of the Costs
  42. 42. Growing Numbers Of Survivors From: The State of Cancer Care in America, 2015: A Report by the American Society of Clinical Oncology. Journal of Oncology Practice 11:JOP.2015.003772–113, 2015
  43. 43. Thank You

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