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Immunotherapy for Breast Cancer

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How can immunotherapy be used to treat metastatic breast cancer? Ian Krop, MD, PhD, discusses the latest research and treatment options.

This presentation was originally given as part of the 2015 Metastatic Breast Cancer Forum, held on October 17 and hosted by the Susan F. Smith Center for Women's Cancers at Dana-Farber Cancer Institute in Boston, Mass.

For more information, visit www.susanfsmith.org

Publicado en: Salud y medicina
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Immunotherapy for Breast Cancer

  1. 1. Immunotherapy in Breast Cancer Ian Krop, MD, PhD Dana-Farber Cancer Institute
  2. 2. Immune system targets • Bacteria • Viruses
  3. 3. Immune system targets • Bacteria • Viruses • Transplanted organs
  4. 4. Immune system targets • Bacteria • Viruses • Transplanted organs • Cancer cells
  5. 5. Courtesy of Erica Mayer
  6. 6. Newsweek 1985
  7. 7. Our immune system has an on/off switch
  8. 8. T-cells are designed to recognize and kill tumor cells
  9. 9. PD-1 acts as an “off-switch” for T-Cells
  10. 10. PD-1/PD-L1 inactivates T-Cells
  11. 11. Antibodies to PD-1 or PD-L1 prevent tumor cells from inactivating T-cells
  12. 12. Antibodies to PD-1 shrinks cancers in the majority of patients with metastatic melanoma
  13. 13. Scott N. Gettinger et al. JCO doi:10.1200/JCO.2014.58.3708 Antibodies to PD-1 are effective in patients with advanced lung cancer
  14. 14. Why such durable responses in very advanced cancers? • Immune system targets many parts of the cancer (antigens) – Harder for cancer to escape recognition • Advanced cancers’ frequent mutations make them more “foreign” to immune system
  15. 15. IMMUNOTHERAPY IN BREAST CANCER
  16. 16. Immune therapy in triple negative cancers • Highest rate of PD-L1 expression • Highest rate of mutations • High level of immune cells in the tumor (TILS)
  17. 17. This presentation is the intellectual property of the presenter, Rita Nanda. Contact rnanda@medicine.bsd.uchicago.edu for permission to reprint and/or distribute. December 9-13, 2014 A Phase Ib Study of Pembrolizumab (MK-3475) in Patients With Advanced Triple-Negative Breast Cancer Rita Nanda,1 Laura Q. Chow,2 E. Claire Dees,3 Raanan Berger,4 Shilpa Gupta,5 Ravit Geva,6 Lajos Pusztai,7 Marisa Dolled-Filhart,8 Kenneth Emancipator,8 Edward J. Gonzalez,8 Jennifer Pulini,8 Kumudu Pathiraja,8 Vassiliki Karantza,8 Gursel Aktan,8 Christine Gause,8 Jonathan Cheng,8 Laurence Buisseret9 1University of Chicago, Chicago, IL; 2University of Washington, Seattle, WA; 3University of North Carolina Lineberger Cancer Center, Chapel Hill, NC; 4Sheba Medical Center, Tel Hashomer, Israel; 5H.Lee Moffitt Cancer Center and Research Institute, Tampa, FL; 6Tel-Aviv Sourasky Medical Center, Tel-Aviv, Israel; 7Yale University School of Medicine, New Haven, CT; 8Merck & Co., Inc., Whitehouse Station, NJ; 9Institut Jules Bordet, Université Libre de Bruxelles, Bruxelles, Belgium
  18. 18. This presentation is the intellectual property of the presenter, Rita Nanda. Contact rnanda@medicine.bsd.uchicago.edu for permission to reprint and/or distribute. December 9-13, 2014 Change From Baseline in Target Lesions Over Time (Central Review) -100 -80 -60 -40 -20 0 20 40 60 80 100 0 8 16 24 32 40 48 56 ChangeFromBaseline,% Time, weeks Analysis cut-off date: November 10, 2014. On treatment Discontinued treatment
  19. 19. Emens LA, et al. AACR, 2015. Inhibition of PD-L1 by MPDL3280A leads to clinical activity in patients with metastatic triple-negative breast cancer (TNBC) Leisha A. Emens,1 Fadi S. Braiteh,2 Philippe Cassier,3 Jean-Pierre DeLord,4 Joseph Paul Eder,5 Marcella Fassò,6 Yan Wang,6 Wei Zou,6 Luciana Molinero,6 Daniel S. Chen,6 Ian Krop7 1Johns Hopkins University, Baltimore, MD; 2Comprehensive Cancer Centers of Nevada, Las Vegas, NV; 3Centre Leon Berard, Lyon, France; 4Institut Claudius Regaud, Toulouse, France; 5Yale School of Medicine, New Haven, CT; 6Genentech, Inc., South San Francisco, CA; 7Dana-Farber Cancer Institute, Boston, MA 21
  20. 20. Emens LA, et al. AACR, 2015. MPDL3280A: Tumor Burden Over Time Efficacy-evaluable population with TNBC 22 • Median duration of response has not yet been reached (range: 18 to 56+ wks) • Median duration of survival follow-up is 40 wks (range: 2+ to 85+ wks) Investigator-assessed confirmed ORRs per RECIST v1.1. Efficacy population includes patients dosed by July 21, 2014; clinical data cutoff, December 2, 2014. New lesions at consecutive visits for the same patient might be the same lesion. CR/PR (n = 4) SD (n = 3) PD (n = 9)
  21. 21. What do these trials tell us? • Provides proof that immunotherapy can work in breast cancer • Important to note that: – Only patients with PD-L1 positive TNBC were included – Only a minority of these patients benefited
  22. 22. Other immunotherapy targets in development Activating Inhibiting Mellman et al. Nature, 2011 Ipilimumab Pembrolizumab Nivolumab
  23. 23. FIRST LINE TNBC Protocol # Short Title 15-241 Phase 3 Abraxane +/- Atezolizumab (anti-PDL1) 15-307 Phase 1/2 Eribulin + Pembrolizumab (anti-PD1) SECOND LINE TNBC 15-240 Phase 2 Pembrolizumab Monotherapy 15-307 Phase 1/2 Eribulin + Pembrolizumab (anti-PD1) Immunotherapy Trials for triple negative breast cancer
  24. 24. Immunotherapy in other breast cancer subtypes • HER2+ – Modest PD-L1 expression – Moderate/high mutational load – Combination of PD-L1 inhibitor and HER2-antibodies are effective in lab studies • ER+ – Low PD-L1 expression – Low mutational load – Likely will need something to increase recognition by immune system
  25. 25. Immunotherapy in other breast cancer subtypes • HER2+ – Modest PD-L1 expression – Moderate/high mutational load – Combination of PD-L1 inhibitor and HER2-antibodies are effective in lab studies • ER+ – Low PD-L1 expression – Low mutational load – Likely will need something to increase recognition by immune system
  26. 26. Planned trials • HER2+ – T-DM1 + anti-PD-1 • ER+ – Eribulin + anti-PD-1 – Preoperative abraxane + anti-PD-1 – Radiation + anti-PD-1
  27. 27. Immunotherapy in Breast Cancer: Summary • Great promise… in other malignancies – Melanoma, lung cancer, lymphoma • Data in breast cancer is very early – Pretreated phase 1 TNBC - exciting data – Larger trials underway – MANY questions remain: • Is PDL1+ prerequisite for activity? • Will benefit be found in TNBC only, or in other subtypes? • Do we need to use drugs targeting other pathways • Much more data in next few years in breast cancer

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