Elacestrant + Everolimus (mTOR) Delivers 8.5 mo PFS After CDK4/6 Failure in ER+/HER2- mBC

Elacestrant, an oral selective estrogen-receptor degrader (SERD), was paired with either everolimus (mTOR inhibitor) or ribociclib (CDK4/6 inhibitor) in the phase 1b/2 ELEVATE umbrella study (NCT05563220). In patients with ER+/HER2- metastatic breast cancer progressing on prior endocrine therapy + CDK4/6i, median PFS reached 8.5 mo for elacestrant 345 mg + everolimus 7.5 mg (22 evaluable) and 7.2 mo for elacestrant 345 mg + ribociclib 400 mg (32 evaluable). Grade ≥3 adverse events were mostly predictable drug-class toxicities—neutropenia 25% with ribociclib; grade ≥3 stomatitis or diarrhea 7% with everolimus—and no new safety signals emerged. For context, single-agent elacestrant after CDK4/6i shows mPFS ≈2.8 mo in EMERALD, everolimus (10mg/day) + exemestane (25mg/day) yields 7.8 mo in BOLERO-2, and switching to ribociclib (600mg/day) after CDK4/6i failure achieves 5.3 mo in the MAINTAIN trial, situating these oral doublets at or above current benchmarks.