abemaciclib + elacestrant

Abemaciclib + elacestrant is an investigational, all-oral combination therapy for the treatment of estrogen receptor–positive (ER+), human epidermal growth factor receptor 2–negative (HER2-) advanced or metastatic breast cancer. Abemaciclib is a selective cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor that blocks cell cycle progression, while elacestrant is an oral selective estrogen receptor degrader (SERD) that antagonizes and degrades the estrogen receptor. The rationale for combining these agents is to overcome endocrine resistance mechanisms and provide a convenient oral regimen for patients who have progressed on prior endocrine therapies, including those with ESR1 mutations or brain metastases. Early-phase clinical trials have demonstrated promising efficacy—such as objective response rates around 15-18%, clinical benefit rates up to 85%, and median progression-free survival of approximately 8.7 months—with a manageable safety profile characterized mainly by low-grade gastrointestinal side effects and neutropenia[2][3][4][5][7].