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Clinical Trials for Metastatic Triple-Negative Breast Cancer

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Overview of clinical trials for metastatic triple-negative breast cancer by Sara M. Tolaney, MD, MPH, Associate Director and Associate Director of Clinical Research at Susan F. Smith Center for Women's Cancers at Dana-Farber Cancer Institute.

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Clinical Trials for Metastatic Triple-Negative Breast Cancer

  1. 1. Clinical Trials for Metastatic Triple-Negative Breast Cancer Sara M. Tolaney, MD, MPH Associate Director Clinical Research
  2. 2. Clinical Trials: Why Participate? • You have a chance to help others and improve cancer care • You can expand the number of treatment options you have • Many trials involve targeted therapies with the goal of improved effectiveness and decreased side effects • If a new treatment is proven to work and you are receiving it, you may be among the first to benefit 2
  3. 3. Clinical Trials: FAQs • When should I consider a clinical trial?  Clinical trials may be an option for you as early as the first treatment you receive for metastatic breast cancer, but may also be an option further into the course of your disease.  If you are interested in trials, getting connected early to a treatment team who can help identify potential trials for you is key. • 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 • 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.
  4. 4. Clinical Trials for Metastatic TNBC • There are many clinical trials open focusing on TNBC. • Clinical trials are testing the safety and effectiveness of new treatments. • Today we will provide some highlights of a few of the available trials. • These treatments are provided as part of trials because we do not understand whether they are the same, better, or worse, than standard treatments. • Trial treatments may also have different side effects than standard treatments. • Each trial has specific requirements for patients to be included. 4
  5. 5. • There are three main subtypes of breast cancer  ER positive  HER2 positive  Triple negative • Within these, there are other ways to further sub-divide breast cancers • Oncologists use the breast cancer subtype to guide the kinds of treatments to recommend • Clinical trials often will focus on specific subtypes Breast Cancer Subtypes
  6. 6. “Triple Negative” Breast Cancer (TNBC) • Defined as negative for estrogen, progesterone, and HER2 receptors • Represents about 15% of all breast cancer • More likely to present in younger women and in women of African ancestry • May be associated with an inherited mutation in BRCA1  National guidelines recommend consideration of genetic testing in women younger than age 60 with TNBC, regardless of family history  But--most patients with triple negative breast cancer do not carry a hereditary BRCA1 mutation
  7. 7. • PD-1 is an inhibitory receptor expressed on immune cells • Tumors express PD-L1 to evade immune surveillance • Interaction between PD-L1 and PD-1 puts the brakes on the immune cells • Antibodies against either receptor takes the brakes off Immunotherapy for TNBC * Thompson et al. 2006; Hamanishi et al. 2007; Okazaki and Honjo 2007; Hino et al. 2010 MHC1 PD-L2 B7-1 PD-L1 TCR PD-1 CD28 B7-1 Antigen Presenting Cell T cell PD-L1 Activation ** Dry, J.R. et al Cancer Research 2010 70;2264; Hoeflich K.P. et al Clin Cancer Res 2009 15(14): 4649 Suppl data. Keir, ME et al 2008. Annu. Rev. Immunol. 26:677
  8. 8. A randomized phase II trial of carboplatin with or without nivolumab in first- or second-line metastatic triple-negative breast cancer
  9. 9. Carboplatin +/- Nivolumab 9
  10. 10. Key Eligibility Criteria • ER and PR ≤ 1% by IHC, and HER2-negative status per ASCO/CAP guidelines. • Measurable or evaluable disease by RECIST version 1.1. • Participants must agree to undergo a research biopsy, if safely accessible, at baseline. • Normal organ and marrow function as defined per protocol • Prior chemotherapy: 0-1 prior chemotherapeutic regimens for MBC; off treatment for at least 14 days prior to registration No prior platinum in the metastatic setting is allowed. Prior platinum in the neo/adjuvant setting is permissible, if ≥ 12 months elapsed since end of adjuvant therapy to development of metastatic disease. If patient recurs within 12 months of neo/adjuvant therapy, this will be counted as one line of therapy for metastatic disease. 10
  11. 11. A few examples of other immunotherapy combination studies • Cabozantinib + nivolumab  Combines a targeted drug that inhibits angiogenesis with an antibody against PD1 • Eribulin + pembrolizumab  Combines chemotherapy with an antibody against PD-1 • Vaccine + pembrolizumab  Combines a peptide vaccine with an antibody against PD-1 11
  12. 12. Drug-Antibody Conjugates for TNBC 12 1. Antibody specific for an antigen on the surface of tumor cells 2. Antibody is linked to a chemotherapy drug 3. Chemotherapy agent is released inside the cancer cell
  13. 13. Phase 2 study of IMMU-132 demonstrated activity in pretreated patients • Response rate=30% in patients with a median of 5 prior therapies since their diagnosis 13
  14. 14. Phase 3 IMMU-132 vs TPC
  15. 15. Key Eligibility Criteria • TNBC per ASCO/CAP criteria, based on the most recent analyzed biopsy or other pathology specimen • Measurable disease by CT or MRI as per RECIST 1.1. Bone-only disease is not permitted • Brain MRI must be done for patients with brain metastasis and patient must have had stable CNS disease for at least 4 weeks • Refractory to or relapsed after >2 prior standard of care chemotherapy regimens for unresectable, locally advanced or metastatic BC.  Regimens will qualify regardless of triple-negative status at the time they were given.  No upper limit in the number of prior chemotherapies.  Earlier adjuvant or neoadjuvant therapy for more limited disease will qualify as one of the required prior regimens if the development of unresectable, locally advanced or metastatic disease occurred within a 12-month period of time after completion of chemotherapy • All patients must have been previously treated with a taxane • Eligible for 1 of the chemo options (Eribulin, capecitabine, gemcitabine, or vinorelbine) per investigator
  16. 16. Other Trial Options • Many other clinical trial options for TNBC  DNA-damaging agents  Cell cycle inhibitors  Other drug antibody conjugates (LIV1)  Trials specific for patients with BRCA mutations 16
  17. 17. How do I find a clinical trial? • Talk with your oncologist and let her/him know you may be interested in clinical trials. • Consider a consultation at an academic cancer center. • • We are also happy to see new patients at Dana-Farber – (617) 632-2175. • Consider web resources. • • Metastatic Breast Cancer Alliance trials-in-metastatic-breast-cancer • Best to ask your oncologist what makes sense for you and to know that this can change over time. 17
  18. 18. How Can We Make Progress? Support Clinical Trials! • “One reason I chose to participate in a clinical trial was to help women with triple-negative breast cancer. It is thanks to women who have enrolled in clinical trials that we have the treatments that give us hope.”  Natalia (LBBC, Guide to Understanding TNBC)