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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 [email protected] 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 [email protected] 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
ovaries) 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!