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

Carey K. Anders, MD

The Presentation Portion of Today’s Program will be Broadcast on FaceBook Live! @KomenNCtriangletothecoast

Carey K. Anders, MD

Welcome

Katrina Cooke

Living with Metastatic Breast Cancer

Thank You to Our Series Sponsors!

Carey K. Anders, MD

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

UNC Lineberger Comprehensive Cancer Center

Carey K. Anders, MD

What is MBC?

Metastasis (noun): The spread of cancer cells from the place in the body where they first formed to another part of the body

• NCI Dictionary of Cancer Terms

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Slide courtesy of Marni S. McClure, PhD

Common Sites of Breast Cancer Metastases: Lung Liver Bone Lymph nodes Brain Ovaries Skin Adrenal glands Other rare sites

Carey K. Anders, MD

Who is affected by MBC?

Mothers Daughters Sisters Cousins Neighbors Friends Co-workers ……

• 150,000 Americans are estimated to be

living with metastatic breast cancer

Mariotto A et al. Cancer Epi Biomarkers 2017

Carey K. Anders, MD

How is MBC treated?

• Systemic Therapy
• Targeted therapy against ER and HER2
• Chemotherapy
• Coming soon….Immunotherapy
• Local Therapy
• Radiation; less commonly surgery

Carey K. Anders, MD

Current Tools in our Toolbox…

An Example in ER+ MBC in 2018

Endocrine Therapies: Letrozole +/- CDK4/6i Tamoxifen Anastrozole Exemestane Fulvestrant Toremifene Megestrol acetate Endocrine-refractory dz: Aromasin/mTORi Fulvestarant +/- CDK4/6i Ethinyl estradiol Chemotherapeutic Regimens Preferred Single Agents: Anthracyclines: Doxorubicin Pegylated liposomal doxorubicin Taxanes: Paclitaxel Anti-metabolites Capecitabine Gemcitabine Other microtubule inhibitors: Vinorelbine Eribulin Other single agents: Cyclophosphamide Carboplatin Docetaxel Ixabepilone Epirubicin Albumin-bound paclitaxel Cisplatin Preferred Doublets: Gem/Taxol

Capecitabine/Docetaxel

Question: How did we get to and expand this list? www.nccn.org

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Drug Discovery:

15 years from lead to market

Research & Preclinical Testing 6.5 years Assess biological activity 5,000 compounds evaluated Clinical Trials Phases I - III 7 years Anticancer activity & toxicity 5 enter trials FDA Approval & Phase IV 1.5 years Review & approval, evaluation of long term effects 1 approved

Source: Regulatory and Scientific Affiars, PhRMA

Carey K. Anders, MD

Drug Discovery: clinical trials

Phase I 1.5 years 20-80 patient volunteers Dosage, Initial toxicity Phase II 2 years 100-300 patient volunteers Evaluate effectiveness, Refine toxicity

Phase III 3.5 years 1,000 to 3,000 patient volunteers Confirm effectiveness, monitor adverse reactions

1.5 years Review process/ Approval Post- marketing safety monitoring Clinical Trials FDA

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A call for clinical trial participation…..!

Barriers: Awareness Location Strict enrollment criteria Time commitment Costs Perceptions

Boromir from Fellowship of the Rings

~5% of Americans participate in clinical trials

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The CDK4/6 inhibitor story….

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Work was ongoing ~2005 with publication 2009

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FDA approval of CDK4/6 inhibitor

Three agents approved in the US:

• 1. Palbocilclib, February 2015
• 2. Ribociclib, March 2017
• 3. Abemaciclib, February 2018

**Each of these anti-cancer agents DOUBLES time until progression of disease

Carey K. Anders, MD

On a personal note….

My mom Aunt SuSu

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Thank you!

Carey K. Anders, MD

The Challenge and Privilege

• f Treating Metastatic Breast Cancer

Sarah Sammons, MD

Duke Cancer Institute / Duke University

Carey K. Anders, MD

Challenges in treating metastatic breast cancer

Optimal sequence therapy Calling progression Side effects of therapy Complications

• f metastatic

breast cancer Navigating clinical trial

• ptions

Psychosocial aspects of living with mBC

Carey K. Anders, MD

Current Treatments in Metastatic HER2+ BC

Sammons; Metastatic HER2+ Breast Cancer, 2018

Carey K. Anders, MD

Current Treatments in Metastatic TNBC

• Chemotherapy
• Chemotherapy
• Chemotherapy
• Chemotherapy
• Parp inhibitors in BRCA carriers

Carey K. Anders, MD

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

• 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.

Carey K. Anders, MD

How Do We Fix This?

• Patient engagement/ advocacy
• Just ASK campaign!
• Lessening constrictive inclusion/exclusion criteria
• Patient advisory counsels
• 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

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How Can We Make Further Progress Faster?

• THINK BIGGER
• COLLABORATE!

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Estrogen and the Immune System

• Estrogens regulate many

aspects of the immune system1, 2

• Women are less likely to

respond to immunotherapy3

• ER+ breast cancer is thought

to be “immunologically cold”

1. Kovats; Horm Behav, 2012. 2. Polancyk; Int. Immunol, 2007. 3. Conforti; Lancet, 2018.

Carey K. Anders, MD

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

“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

Carey K. Anders, MD

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 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

Carey K. Anders, MD

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 (c) inform optimal immune therapy/ ERα modulator combinations

Carey K. Anders, MD

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
• Sharing in their frustration; being in a position to attempt change
• Offering novel treatments/ hope

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THANK YOU

Collaborators

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The Patient Perspective

Rhonda Howell

Living with Metastatic Breast Cancer

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Research Overviews

Katie Hoadley, PhD

UNC Lineberger Comprehensive Cancer Center

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• Dr. Michael Emmanuele, PhD

Assistant Professor, UNC Chapel Hill FY14 CCR Basic/Translational Award

Research Overviews

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• Dr. Zachary Hartman, PhD

Assistant Professor, Duke University FY14 CCR Basic/Translational Award

Research Overviews

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Dana Grant, MS

NC Central University FY16 Graduate Training in Disparities Research Award

Research Overviews

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• Dr. Susana Garcia Recio, PhD

UNC Chapel Hill FY17 Postdoctoral Fellowship Award

Research Overviews

Carey K. Anders, MD Dr. Erika Crosby, PhD

Duke University FY17 Postdoctoral Fellowship Award

Research Overviews

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Roundtable Discussion

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Closing Remarks

Pam Kohl

Living with Metastatic Breast Cancer

Join the Fight. Save Lives.