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Moving Beyond Resistance: Current Research in ER+ Metastatic Breast Cancer

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A look at the new and exciting treatment options that are on the horizon for metastatic ER+ breast cancer.

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Moving Beyond Resistance: Current Research in ER+ Metastatic Breast Cancer

  1. 1. Moving Beyond Resistance: Current Research in ER+ Metastatic Breast Cancer Heather A. Parsons Dana-Farber Cancer Institute Harvard Medical School September 24, 2016
  2. 2. Hormonal therapy Hormonal therapy Chemotherapy ChemotherapyHormone receptor positive How Do We Treat Metastatic Breast Cancer?
  3. 3. Some Questions to Answer in Metastatic ER+ Breast Cancer • Why do some tumors never respond to a particular treatment? • Why do most tumors eventually develop resistance to a particular treatment? • How do we develop better treatments for metastatic ER+ breast cancer?
  4. 4. Demand for Precision Medicine President Obama launched the Precision Medicine Initiative (PMI) in January 2015 to accelerate “biomedical discoveries and provide clinicians with new tools, knowledge, and therapies to select which treatments will work best for which patients.” Precision medicine is enabling a new era of clinical care through research, technology, and policies that empower patients, researchers, and providers to work together toward development of individualized care. Advancing the science of medicine also calls for a change in the culture of medical practice and medical research to engage individuals as active collaborators – not just as patients or research subjects.
  5. 5. Designed to obtain genomic information on all patients who come to DFCI / BWH / BCH for cancer-related care Goals: • Collect genomic information on all patients who have cancer, are presumed to have cancer, or are at risk for developing cancer • Return clinically relevant results to providers • Store results in searchable database • Enable linkage of specimen results to clinical database PROFILE: Towards Precision Cancer Medicine Since August 2011, >30,000 patients have consented (75%) and >12,000 tests have been performed
  6. 6. Metastatic tumor biopsy & blood samples PROFILE (Targeted Sequencing) Additional Molecular Studies and Banking Make Cell Line Models and Mouse Models Studies of Resistance /Discovery of New Targets Experimental Studies Pathology ER, PR, HER2 Returned to Physician for Clinical Decision Making Comprehensive Next Generation Sequencing (Whole Exome and Transcriptome Sequencing) Center for Cancer Precision Medicine (CCPM) ER+ Metastatic Breast Cancer Study Future Uses “Blood” or “Liquid” Biopsies
  7. 7. Metastatic tumor biopsy & blood sample Patients with metastatic ER+ breast cancer with resistance to endocrine therapy Clinical Trials of Novel Agents and Combinations Specific to Identified Resistance Mechanisms Trial #1 (e.g. novel SERD) Trial #2 (e.g. PI3Ki combo) Trial #3 (e.g. CDKi combo) Future Trials (to be developed) COMPREHENSIVE SYSTEMATIC TUMOR ANALYSIS Center for Cancer Precision Medicine (CCPM) ER+ Metastatic Breast Cancer Study
  8. 8. Circulating tumor DNA (ctDNA) • Metastatic biopsies can be challenging • Cancer (and normal) cells shed ctDNA into blood • ctDNA could identify markers of drug sensitivity or resistance in a cancer
  9. 9. ESR1 Mutations in Previously Treated ER+ Breast Cancer
  10. 10. ESR1 mutations in ctDNA predict benefit for Fulvestrant vs. Exemestane Charlotte Fribbens et al. JCO doi:10.1200/JCO.2016.67.3061 ©2016 by American Society of Clinical Oncology
  11. 11. ctDNA in EMBRACE • ctDNA could identify tumor alterations to direct patients to a trial • ctDNA may show tumor alterations that are mechanisms of treatment resistance
  12. 12. Selective Estrogen Receptor Degraders (SERDs) • Estrogen signaling: – Essential for ER+ breast cancer cell growth • SERDs bind/block ER • Overcome ESR1 mutation mediated resistance • Oral SERDs in trials
  13. 13. Inhibition of PI3K • PI3K pathway very often altered in breast cancer • Responsible for many essential cell activities: – Growth promotion, energy creation, etc. • Multiple PI3Ki in clinical trials currently
  14. 14. Selective Androgen Receptor (AR) Modulators • AR drives cancer cell growth • SARMs may be effective, have few side effects • Clinical trials are available for SARMs
  15. 15. How Can We Do Better? Participate in Trials! • Clinical trials exist for patients at any step of their breast cancer journey; trials are a part of the continuum of care • There are benefits to being on a trial! – a larger treatment team – possible exposure to cutting edge new medications – helping other patients with breast cancer • None of the advances in breast cancer could have happened without patients volunteering to be in trials!
  16. 16. What are clinical trial phases? Clinical trials are conducted in a series of steps (phases) - each phase is designed to answer a separate research question. • Phase I: Testing a new treatment in a small group to evaluate safety, dose, and side effects. • Phase II: Evaluating within a larger group the efficacy and safety of a new treatment • Phase III: A comparison study in a large group to determine if a new treatment works better than standard therapy. These trials typically involve randomization and may have a placebo; the data from a phase 3 trial can be used for FDA drug approval. FDA
  17. 17. How Do I Enter a Trial? • Your provider will discuss with you trials of interest, review rationale, as well as risks and benefits • A research RN will review a consent form with you, which describes the structure and details of the trial • After a consent is signed, there is a “screening” period to determine if you are eligible • When eligibility is confirmed, then you register and can begin trial therapy
  18. 18. Clinical Trials: FAQs • If I consent to a trial, do I have to stay on it? – You can leave a trial at any time if either you or your provider thinks being on the trial is no longer in your best interest • Will I have to pay more to be on a trial? – All normal procedures are billed to insurance; anything beyond normal care is paid for by the trial. There should be no “upcharge” for being in a trial • Is being on a trial busy? – Each trial is different and has a different schedule • Will I know what medicine I am getting? I don’t want a placebo. – In most trials, both patient and provider know exactly what treatment is being given. – Some larger trials use randomization and placebos, and in some cases neither patient nor provider know identity of study drug. – But in almost every trial with placebo, at minimum a patient receives best standard of care.
  19. 19. Conclusion • New, exciting treatment options are on the horizon for metastatic ER+ breast cancer • Metastatic biopsies and blood sampling may help direct individual patients’ treatment and help us move toward new, better treatments • Clinical trials allow access to new therapies and help us make progress

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