ASCO 2014Metastatic breast

cancerDon S. Dizon

Massachusetts General Hospital

Harvard Medical School

Three themes

• Supportive care news:• Zoledronic acid• Early palliative care • Vaginal DHEA

• Novel therapeutic approaches to watch for:• Immunotherapy• Targeted therapy

• National and ASCO initiatives of particular relevance:• Quality, Value, and You

Source: http://understandcancerin60minutes.wordpress.com/2013/12/12/surgical-removal-of-primary-tumor-and-axillary-nodes-in-women-with-metastatic-breast-cancer/comment-page-1/

Zoledronic acid: Every 12 weeks is AOK

• OPTIMIZE-2 trial• Over 400 women with MBC and bone metastases• Stable for approximately one year on monthly IV bisphosphonate

treatment• RANDOMIZATION: Zoledronic acid every 4 versus 12 weeks• Primary outcome:

• Rate of skeletal related events (SRE)• Time to first on-study SRE

• RESULTS:• No difference in SRE rate: 22% versus 23%• No difference in time to first SRE • Only 2 cases of jaw osteonecrosis seen (both with every 4 week

treatment)Hortobagyi G, et al. LBA9500

Managing bone metastases

Agent Formulation

Denosumab (D) SQ injection

Bisphosphonates (IV) Zoledronic acid (ZA) Pamidronate (P)

IV

Bisphosphonates (PO) Clodronate Ibandronate

Oral

• Comparing effectiveness:• D is better than ZA• ZA is better than P• IV is better than PO

• Comparing toxicity:• P and ZA require infusion• P >> ZA to infuse• Low rates of ONJ

• Comparing cost:• D >> ZA >> P • PO not available in the US

Managing bone metastases: OPTIMIZE-2

• If you are stable on monthly treatment for at least 1 year:• Continue Denosumab (every 4 weeks)• PRO: Convenience of administration• CON: Expensive

• Change to Zoledronic acid (every 12 weeks)• PRO: Convenience of schedule• CON: IV infusion

Bisphosphonates do not influence survival

A positive trial for survival

•One trial showed that a research intervention resulted in:• Improvement in OS

at one year• Improvement in

median OS

ENABLE-3

• ENABLE: Educate, Nurture, Advise, Before Life Ends

• Arms:• Intevention: Immediate palliative care 3 months after a diagnosis of

advanced cancer • Concurrent palliative care with oncology care• Standard of care: Palliative care done at 12 weeks

• Intervention: PC Consult in person then 6 Telephone based interventions• Aimed at both Patient and their caregiver

• Population: Lung (44%), GI (25%), Breast (10%)

Bakitas M, et al. Abstr 9512

The Intervention

ENABLE-III Intervention

Palliative-care consult

Charting your course (Telephone)

-- What is palliative care? Problem solving, coping

-- Self-care and Symptom management

-- Communication, Decision-Making, Advance Care Planning

-- Life Review

-- Forgiveness

-- Creating a Legacy

What did not change?

• Intervention had no significant impact on:•Depression scores• Resource utlization including:• Hospital days (5 vs 6 days)• ICU days (median in both groups was 0)• ED visits (median in both groups was 1)• Chemo in the last 2 weeks of life (4 vs 3

patients)

Palliative care is important

• Second randomized trial showing a survival benefit• ENABLE-3: QOL benefit extended to caregivers (LBA9513)• Issues:• When is it appropriate (survivorship versus

palliative care)• Palliative care = hospice care (NO)

Communication is key

• Survivorship = Prevention and treatment of complications• Palliative care = Proactive attention to symptoms• Symptoms span medical realm: Psychosocial,

Spiritual, Emotional

• It’s all about SUPPORT

Relief for sexual dysfunction: Vaginal DHEA

• ASCO 2014: Barton, et al. • RCT (Alliance N10C1)• Women with breast or gyn cancer (n=441)• Vaginal DHEA (3.25 v 6.5 mg) versus placebo• Results:

• All 3 arms had improvement in symptoms• At 12 weeks, DHEA improved sexual satisfaction significantly

• Effect size based on FSFI: +0.3-0.6• Side effects with DHEA: voice change, headache

Presented by: Don S Dizon MD

Therapeutic news

•No results that will add to or change standard of care• Important directions from other malignancies to be gained•Molecular therapy, work is preliminary

Potential in MBC?

Treatment Data from ASCO 2014

Immunotherapy Melanoma (LBA9008, 9000-9003): Ipilimumab, NivolumabEarly-stage breast cancer (Abstr 1098): Cryoablation + Ipilimumab

T-cell therapy Cervical cancer (LBA3008): Activated T-cells in HPV+ cervical cancer

Chemohormonal therapy

Prostate cancer (Docetaxel plus adrogen deprivation therapy in metastatic prostate cancer)

Combination therapy

Ovarian cancer (LBA 5500): Phase II of cediranib (angiogenesis inhibitor) plus olaparibBreast cancer (Abstr 2510): Phase I of PI3K inhibitor (BKM1120) plus olaparib

Studies of note

• Phase IB/II in ER+/HER2- MBC: Abstr 535 • LEE011 (CDK4/6 inhibitor) – doses being escalated on 3w on/1w off

basis• Everolimus (mTOR inhibitor) – continuous• Exemestane – continous• No efficacy data (only 6 patients enrolled)

• Phase I in HER2+MBC: Abstr TPS672• T-DM1• BYL719 (PI3K-inhibitor)• Ongoing for patients with PD after Trastuzumab plus taxane

No data at ASCO: Implications for MBC

• Studies are ongoing• Expect more data in future congresses

• 3rd International Congress on Personalized Medicine (June 2014)

• Novel Cancer Therapeutics Summit (July 2014)• International Assn for Breast Cancer Research

Conference (September 2014)• Breast Cancer Symposium (September 2014)• San Antonio Breast Cancer Symposium (December 2014)

Quality in Oncology

Clinically meaningful outcomes is an ASCO initiative

• Costs are going up

• Defining efficacy is non-standard

• Reports of toxicity are not consistent

J Clin Oncol 2014; 12: 1277

ASCO

• Working groups to determine clinically meaningful outcomes• Objective: establish consensus among experts • Consensus view: “Relative improvement in median

OS of at least 20% are necessary to define a clinically meaningful improvement in outcome.”• Scenario of these viewpoints:• Metastatic disease, receiving first-line systemic

treatment

ASCO: Viewpoint on Targets

What ASCO paper is NOT

•Not a recommendation•Not a guideline•Not criteria for drug approval•Not to be used to make decisions on current treatment

What ASCO paper IS

• An example of how clinical trials should be designed• A Call to Arms for:• Patients• Patient Advocates• Clinical investigator

• Call: DEMAND better, RAISE expectations

“The outcomes discussed here can only be considered aspirational at this time”

What this means for patients with MBC

• No changes to standard treatment and how decisions on your care are made.

• There is nothing new re: dilemma of costs/toxicity/efficacy

The Bottom Line

• Potential therapeutic interventions expanding• Cancer = chronic disease•We all must define clinical meaningfulness.• Do not assume this is cost alone

• Engage• Become empowered• Collaborate

Quality of Care is important

Project launched on Cosano crowdsourcing platform

What is the role of preventative medicine for patients already living with metastatic breast cancer

Big data project using MGH datasets

Quality of Care is important

Goals:• Describe how preventative methods (mammography,

colonoscopy, pap smears, aspirin use, screen for dyslipidemia) are used in women with advanced or metastatic breast or ovarian cancer• Determine if there are women who would benefit from

preventative screening

To support this project, visit consano.org

Thank you

@drdonsdizon