Johns Hopkins Clinical Update Webinar Ben Ho Park, M.D., Ph.D. - - PowerPoint PPT Presentation

Johns Hopkins Clinical Update Webinar

Ben Ho Park, M.D., Ph.D. Department of Oncology Johns Hopkins University February 2015

This presentation is the intellectual property of the author/presenter. Contact bpark2@jhmi.edu for permission to reprint and/or distribute.

Disclosure Information

• I have the following financial relationships to

disclose though none are relevant to this seminar

• Consultant for Novartis
• Scientific Advisory Board Member for Horizon Discovery,

LTD

• Royalties from Horizon Discovery, LTD
• SAB for Loxo Oncology
• Research contract with Genomic Health, Inc.
• Research contract with Foundation Medicine

This presentation is the intellectual property of the author/presenter. Contact bpark2@jhmi.edu for permission to reprint and/or distribute.

What’s new in breast cancer????

• New studies affecting treatment options for pre-menopausal women

with ER positive disease

• A newly approved therapy for post-menopausal women with ER

positive metastatic disease

• Possible “new” therapies for triple negative breast cancers with early

stage disease

• New therapies on the horizon

Ovarian suppression and aromatase inhibitors for premenopausal women with early stage ER positive breast cancer

• Early stage patients are treated with surgery and/or radiation for local

disease

• If ER positive, then women are likely to be recommended

endocrine/hormone therapy for 5 to 10 years

• For premenopausal women, tamoxifen is still standard of care
• For postmenopausal women, aromatase inhibitors (AI) have become

standard of care because they work a bit better

• If we suppress ovarian production of estrogen, and then give AI, is

that better than tamoxifen?

Suppression of Ovarian Function Trial and Tamoxifen and Exemestane Trial (SOFT and TEXT)

• Combined analysis of thousands of pre-menopausal women

undergoing endocrine therapy after surgery ± radiation for early stage ER positive breast cancer

• Comparing ovarian suppression (OS; or surgery or radiation to
• varies) with tamoxifen vs OS with AI (SOFT and TEXT) vs. tamoxifen

alone (SOFT)

• About 5 years of follow up for these analyses.
• Results are that OS with AI is slightly better at 5 years to reduce

recurrence in women

Is this “the” new standard of care

• Benefit of OS+AI is slight, and more obvious in higher risk women

who received chemotherapy

• Side effect profiles are higher (osteoporosis; muscle/joint pain) in

women with OS+AI

• No convincing overall survival data yet; too short of follow up
• Therefore this is an option as “another” standard of care
• Longer term follow up is key; 10 years of tamoxifen is better than 5,

but at 7 years this difference was not seen

Palbociclib-Ibrance

• Inhibits key proteins involved with “cell cycling” or cell proliferation

(cdk4/6)

• Seems to be limited to ER positive disease – reasons are unclear
• Studied mostly in ER positive metastatic disease and with AI

(letrozole)

• PALOMA1, 2 and 3
• Improvement in progression free survival (~10 months vs. ~20 months)
• Side effects include low blood counts, fatigue
• Very costly

Palbociclib

• Only for post-menopausal women (studied in this population with

letrozole)

• Only for HER2 negative patients with ER/PR positive disease
• Only for first line endocrine based therapy (for now)

Early stage triple negative disease

• Breast cancers without ER/PR/HER2 receptors “triple negative breast

cancers; TNBC”, are more aggressive cancers, but tend to respond better to chemotherapies

• Some studies in the neoadjuvant setting (chemotherapy before

surgery) suggest women with TNBC may respond better to platinum based chemotherapies (cisplatin, carboplatin)

• Definitive large studies being planned to confirm this notion

Early stage triple negative disease

• If confirmed, it may be that for early stage TNBC, women will receive

three to four drugs after surgery, one of which is a platinum drug

• Many oncologists are starting to use platinum based drugs before

surgery or after surgery for TNBC, but this is not standard of care (yet)

• Some evidence suggests BRCA1 and 2 related cancers may have

better response to platinum based chemotherapy regimens

New therapies on the horizon

• Newer CDK inhibitors for ER positive disease
• Combination of CDK inhibitors with tamoxifen, OS+AI
• Vaccine approaches for TNBC
• Newer HER2 directed therapies using pills and antibody based drug

delivery

• Newer endocrine therapies that may overcome resistance to

mutations in estrogen receptor?

• Immunotherapies or “checkpoint inhibitors” to try and “turn on” the

body’s immune system against cancer cells

Conclusions

• There continues to be new therapies for all types and stages of breast

cancer

• Research into how cancers arise and develop drug resistance has led

to these advances

• Breast cancers are all different, so treating with individualized therapy

is the goal of the future

• Thanks!