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 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!
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