SABCS 2017 - Breast Cancer

The new oral selective estrogen receptor degrader (SERD) elacestrant demonstrates potent antitumor activity in in vitro models, with additive effects to CDK4/6 inhibitors.
CDK6 may be a useful biomarker in patients with estrogen receptor–positive breast cancer who develop acquired resistance to CDK4/6 inhibitors, and inhibition of the PI3K/Akt/mTOR pathway may be a reasonable therapeutic approach for these patients.
An underlying mechanism of combined endocrine therapy and CDK4/6 inhibitor resistance in hormone receptor–positive breast cancer is senescent escape, and 2 novel therapeutic strategies have been identified for this disease, including MDM2 inhibition and CDK2 activation.
Although there are currently no biomarkers to guide the use of CDK4/6 inhibitors for estrogen receptor (ER)-positive breast cancer, markers of mismatch repair dysregulation could identify patients in whom CDK4/6 inhibition may prevent disease recurrence most effectively.
The phase 1b trial of the insulin-like growth factor ligand-neutralizing antibody xentuzumab and the CDK4/6 inhibitor abemaciclib, plus endocrine therapy, is designed to evaluate safety, tolerability, and preliminary efficacy in patients with locally advanced or metastatic hormone receptor (HR)-positive/HER2-negative breast cancer.
Dr Matthew Goetz addresses the prospect of utilizing CDK4/6 inhibitors to treat patients with HER2+ metastatic breast cancer, stating early data indicate that CDK4/6 inhibitors may have some antitumor activity in HER2+ breast cancer.
Despite international guidelines and data that show CDK4/6 inhibitors plus aromatase inhibitors can improve overall response rates, overall survival, and progression-free survival in patients with metastatic breast cancer, there is a lasting belief among patients that chemotherapy is the preferable course of treatment. Dr. Hope Rugo attempts to dispel this misconception, citing that endocrine therapy and CDK4/6 inhibitors are well tolerated and don’t have the intensive side effects associated with chemotherapy.
A comparison of the relative efficacy of combination hormone therapies in hormone receptor‒ positive/HER2-negative metastatic breast cancer (MBC) suggests that everolimus/exemestane may be the most effective treatment option available.
Triplet therapy consisting of an mTOR inhibitor, a CDK4/6 inhibitor, and an estrogen receptor (ER) antagonist such as fulvestrant may be optimal in treating hormone receptor–positive metastatic breast cancer, especially in the setting of CDK4/6-resistant tumors.
Radius Health, Inc. (Nasdaq:RDUS) today provided an update on data from the Phase 1 005 clinical study of elacestrant (RAD1901), an oral selective estrogen receptor degrader (SERD), in patients with estrogen receptor positive (ER+) breast cancer. The data were presented at a Spotlight Presentation (Abstract 1410) during the 2017 San Antonio Breast Cancer Symposium (SABCS). Elacestrant recently received Fast Track designation from the U.S. Food and Drug Administration.
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