Uploaded byDana-Farber Cancer Institute
Immunotherapy for Breast Cancer
The document discusses the potential of immunotherapy in breast cancer, particularly in triple-negative breast cancer (TNBC), highlighting the role of PD-1/PD-L1 inhibitors. It presents findings from studies showing that these therapies can lead to significant tumor shrinking in some patients, though typically only those with PD-L1 positive tumors benefit. The document also addresses the need for further research and trials to fully understand the effectiveness of immunotherapy across various breast cancer subtypes.
More Related Content
Similar to Immunotherapy for Breast Cancer
More from Dana-Farber Cancer Institute
Immunotherapy for Breast Cancer
- 1. Immunotherapy in BreastCancer Ian Krop, MD, PhD Dana-Farber Cancer Institute
- 2. Immune system targets •Bacteria • Viruses
- 3. Immune system targets •Bacteria • Viruses • Transplanted organs
- 4. Immune system targets •Bacteria • Viruses • Transplanted organs • Cancer cells
- 5. Courtesy of EricaMayer
- 6.
- 8. Our immune systemhas an on/off switch
- 9. T-cells are designedto recognize and kill tumor cells
- 10. PD-1 acts asan “off-switch” for T-Cells
- 11.
- 12. Antibodies to PD-1or PD-L1 prevent tumor cells from inactivating T-cells
- 14. Antibodies to PD-1shrinks cancers in the majority of patients with metastatic melanoma
- 15. Scott N. Gettingeret al. JCO doi:10.1200/JCO.2014.58.3708 Antibodies to PD-1 are effective in patients with advanced lung cancer
- 16. Why such durableresponses 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
- 17. IMMUNOTHERAPY IN BREASTCANCER
- 18. Immune therapy intriple negative cancers • Highest rate of PD-L1 expression • Highest rate of mutations • High level of immune cells in the tumor (TILS)
- 19. This presentation isthe intellectual property of the presenter, Rita Nanda. Contact [email protected] 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
- 20. This presentation isthe intellectual property of the presenter, Rita Nanda. Contact [email protected] 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
- 21. Emens LA, etal. 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
- 22. Emens LA, etal. 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)
- 23. What do thesetrials 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
- 24. Other immunotherapy targetsin development Activating Inhibiting Mellman et al. Nature, 2011 Ipilimumab Pembrolizumab Nivolumab
- 25. 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
- 26. Immunotherapy in otherbreast 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
- 27. Immunotherapy in otherbreast 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
- 28. Planned trials • HER2+ –T-DM1 + anti-PD-1 • ER+ – Eribulin + anti-PD-1 – Preoperative abraxane + anti-PD-1 – Radiation + anti-PD-1
- 29. Immunotherapy in BreastCancer: 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
Editor's Notes
- #6 Its been 50 years since one fo the first observations of the compex interplay between cancer and the immune system
- #16 Clinical activity in patients with non–small-cell lung cancer (NSCLC) receiving nivolumab. Kaplan-Meier curves of overall survival (OS) for (A) total patient population (N = 129) and (B) patients who received nivolumab 1 (n = 33), 3 (n = 37), or 10 mg/kg (n = 59). Symbols indicate censored events, defined for OS as time to last known date alive before date of data analysis, for patients without death. (C) Tumor burden kinetics in patients with NSCLC treated with nivolumab 3 mg/kg (n = 37). Baseline tumor measurements are standardized to zero. Tumor burden was measured as sum of longest diameters of target lesions compared with baseline. Red triangles indicate first occurrence of new lesion. Horizontal dashed line at −30% indicates threshold for defining objective response (partial tumor regression) in absence of new lesions or nontarget disease progression, according to RECIST (version 1.0); vertical dashed line at 96 weeks indicates protocol-defined maximum duration of continuous nivolumab therapy. (D) Characteristics of objective responses in patients with squamous cell histology (n = 9) and nonsquamous cell histology (n = 13) treated with nivolumab. Vertical dashed line at 22 months indicates maximum planned duration of continuous nivolumab therapy. Eighteen responders discontinued nivolumab therapy for reasons other than disease progression, including: completion of maximum cycles (n = 7), adverse events (n = 8), withdrawal of consent (n = 2), and other (n = 1).