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!