Program will be Broadcast on FaceBook Live! Carey K. Anders, MD - PowerPoint PPT Presentation

The Presentation Portion of Today’s Program will be Broadcast on FaceBook Live! Carey K. Anders, MD @KomenNCtriangletothecoast

Welcome Carey K. Anders, MD Katrina Cooke Living with Metastatic Breast Cancer

Thank You to Our Series Sponsors!

https://www.youtube.com/watch?v=P6HAN-XAcnI Carey K. Anders, MD

Metastatic Breast Cancer: “The What, the Who, the How and a Pathway Forward” Carey K. Anders, MD Carey K. Anders, MD UNC Lineberger Comprehensive Cancer Center

What is MBC? Metastasis (noun): The spread of cancer cells from the place in the body where they first formed to another Carey K. Anders, MD part of the body - NCI Dictionary of Cancer Terms

Common Sites of Breast Cancer Metastases: Lung Liver Bone Lymph nodes Carey K. Anders, MD Brain Ovaries Skin Adrenal glands Other rare sites Slide courtesy of Marni S. McClure, PhD

Who is affected by MBC? • 150,000 Americans are estimated to be living with metastatic breast cancer Mothers Daughters Carey K. Anders, MD Sisters Cousins Neighbors Friends Co-workers …… Mariotto A et al. Cancer Epi Biomarkers 2017

How is MBC treated? • Systemic Therapy - Targeted therapy against ER and HER2 - Chemotherapy - Coming soon….Immunotherapy Carey K. Anders, MD • Local Therapy - Radiation; less commonly surgery

Current Tools in our Toolbox… An Example in ER+ MBC in 2018 Chemotherapeutic Regimens Endocrine Therapies: Other single agents: Preferred Single Agents: Letrozole +/- CDK4/6i Cyclophosphamide Anthracyclines: Tamoxifen Carboplatin Doxorubicin Anastrozole Docetaxel Pegylated liposomal Exemestane Ixabepilone doxorubicin Carey K. Anders, MD Fulvestrant Epirubicin Taxanes: Toremifene Albumin-bound Paclitaxel Megestrol acetate paclitaxel Anti-metabolites Cisplatin Capecitabine Endocrine-refractory dz: Gemcitabine Aromasin/mTORi Other microtubule Preferred Doublets: Fulvestarant +/- CDK4/6i inhibitors: Gem/Taxol Ethinyl estradiol Vinorelbine Capecitabine/Docetaxel Eribulin www.nccn.org Question: How did we get to and expand this list?

Drug Discovery: 15 years from lead to market Clinical Trials Research & FDA Approval & Phases I - III Phase IV Preclinical Testing 6.5 years 7 years 1.5 years Carey K. Anders, MD Assess biological Anticancer Review & approval, activity & evaluation of activity toxicity long term effects 5,000 compounds 5 enter 1 approved evaluated trials Source: Regulatory and Scientific Affiars, PhRMA

Drug Discovery: clinical trials Clinical Trials FDA Phase II Phase III Phase I 3.5 years 1.5 years 2 years 1.5 years 1,000 to 100-300 20-80 Review 3,000 Carey K. Anders, MD patient patient process/ patient volunteers volunteers Approval volunteers Dosage, Evaluate Post- Confirm effectiveness, Initial marketing effectiveness, Refine toxicity safety monitor adverse toxicity monitoring reactions

A call for clinical trial participation…..! ~5% of Americans participate in clinical trials Barriers: Carey K. Anders, MD Awareness Location Strict enrollment criteria Time commitment Costs Boromir from Fellowship of the Rings Perceptions

The CDK4/6 inhibitor story…. Carey K. Anders, MD

Carey K. Anders, MD Work was ongoing ~2005 with publication 2009

FDA approval of CDK4/6 inhibitor Three agents approved in the US: 1. Palbocilclib, February 2015 2. Ribociclib, March 2017 Carey K. Anders, MD 3. Abemaciclib, February 2018 **Each of these anti-cancer agents DOUBLES time until progression of disease

On a personal note…. Carey K. Anders, MD My mom Aunt SuSu

Thank you! Carey K. Anders, MD

The Challenge and Privilege of Treating Metastatic Breast Cancer Carey K. Anders, MD Sarah Sammons, MD Duke Cancer Institute / Duke University

Optimal sequence therapy Psychosocial aspects of Calling living with progression mBC Challenges in treating metastatic Carey K. Anders, MD breast cancer Navigating Side effects of clinical trial therapy options Complications of metastatic breast cancer

Current Treatments in Metastatic HER2+ BC Carey K. Anders, MD Sammons; Metastatic HER2+ Breast Cancer, 2018

Current Treatments in Metastatic TNBC • Chemotherapy • Chemotherapy Carey K. Anders, MD • Chemotherapy • Chemotherapy • Parp inhibitors in BRCA carriers

Carey K. Anders, MD

Challenges Among Clinical Trials • Only 1/20 adults participate in cancer clinical trials in the US • 20% of trials close because they cannot get enough participants • Carey K. Anders, MD 86% do not meet recruitment in projected time frame • Disparities exist in recruitment, retention and trust in clinical trials and biorepositories (adults with low socioeconomic status, racial and ethnic minority groups and those who live in rural areas) Am Soc Clin Oncol Educ Book. 2017;37:139-143. doi: 10.14694/EDBK_179807.

How Do We Fix This? • Patient engagement/ advocacy • Just ASK campaign! • Lessening constrictive inclusion/exclusion criteria • Patient advisory counsels Carey K. Anders, MD • Formation of Duke Cancer Institute patient and community registry • Improving online tools that are patient friendly • Involving community oncology practices in research • Merge trial information with electronic medical record

How Can We Make Further Progress Faster? • THINK BIGGER • COLLABORATE! Carey K. Anders, MD

Estrogen and the Immune System • Estrogens regulate many aspects of the immune system 1, 2 • Women are less likely to Carey K. Anders, MD respond to immunotherapy 3 • ER+ breast cancer is thought to be “immunologically cold” 1. Kovats; Horm Behav, 2012. 2. Polancyk; Int. Immunol, 2007. 3. Conforti; Lancet, 2018.

Treatment of Estrogen Driven Breast Cancers • Current goal is extreme estrogen deprivation • Impact of SOC endocrine therapies on host immunity is unknown • All women with metastatic ER+ breast cancer eventually become Carey K. Anders, MD “endocrine resistant” We have hypothesized that decreasing estrogen could have unintended negative consequences on host immunity which is an ultimate barrier to cure in early stage and advanced ER+ breast cancer

Endocrine Therapy Impact of Host Immunity in Early Stage ER+ Disease 110 Pre- and post-menopausal women with early stage estrogen receptor positive (ER+) breast cancer s/p definitive surgery AND metastatic patients starting CDK4/6 inhibitors +/- endocrine therapy Carey K. Anders, MD Patients enrolled prior to starting endocrine therapy (ET)  Specific cohorts identified to optimally access differences in the effect of ET in the adjuvant setting as a function of age, menopausal status, and type of ET  Peripheral blood mononuclear cells (PBMCs), estrone and estradiol levels collected at baseline and 4, 12, and 24 weeks after ET; archival tissue from surgical specimen will be collected

Study AIMS (a) establish the impact of endocrine therapies on the immune system in relation to changing estrogen levels (b) identify the activities of endocrine therapies on host immunity that need to be improved to increase efficacy Carey K. Anders, MD (c) inform optimal immune therapy/ ERα modulator combinations

Targeting the Immune System and DNA Damage Repair in Platinum-Sensitive TNBC Carey K. Anders, MD

The Privileges of Treating Metastatic Breast Cancer • The women • Their families • Sharing in their joy Carey K. Anders, MD • Sharing in their frustration; being in a position to attempt change • Offering novel treatments/ hope

THANK YOU Collaborators Carey K. Anders, MD

The Patient Perspective Rhonda Howell Carey K. Anders, MD Living with Metastatic Breast Cancer

Research Overviews Katie Hoadley, PhD Carey K. Anders, MD UNC Lineberger Comprehensive Cancer Center

Research Overviews Dr. Michael Emmanuele, PhD Carey K. Anders, MD Assistant Professor, UNC Chapel Hill FY14 CCR Basic/Translational Award

Research Overviews Dr. Zachary Hartman, PhD Carey K. Anders, MD Assistant Professor, Duke University FY14 CCR Basic/Translational Award

Research Overviews Dana Grant, MS Carey K. Anders, MD NC Central University FY16 Graduate Training in Disparities Research Award

Research Overviews Dr. Susana Garcia Recio, PhD Carey K. Anders, MD UNC Chapel Hill FY17 Postdoctoral Fellowship Award

Research Overviews Carey K. Anders, MD Dr. Erika Crosby, PhD Duke University FY17 Postdoctoral Fellowship Award

Roundtable Discussion Carey K. Anders, MD

Closing Remarks Pam Kohl Carey K. Anders, MD Living with Metastatic Breast Cancer

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