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.
The combination of abemaciclib plus anastrozole is superior to anastrozole alone in reducing Ki67 across a spectrum of subgroups of patients with hormone receptor (HR)-positive, HER2-negative breast cancer.
Abemaciclib, but not ribociclib or palbociclib, exhibits inhibition of CDK4/6 plus kinases other than CDK4/6, and induces cell death rather than cytostasis, which may be therapeutically advantageous in patients with hormone receptor‒positive breast cancer that is generally resistant to CDK4/6 inhibitors.
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