The progression of estrogen receptor–positive, HER2-negative metastatic breast cancer after first-line endocrine therapy (ET) and CDK4/6 inhibitors is often driven by resistance mechanisms, such as acquired ESR1 mutations. The phase 3 EMERALD trial previously demonstrated the efficacy of elacestrant as a single agent in improving progression-free survival (PFS) compared with standard-of-care (SOC) ET in patients with prior ET plus CDK4/6 inhibitors. Building on this, the phase 1b/2 ELEVATE trial evaluated the safety and efficacy of elacestrant in combination with ribociclib or everolimus to address different resistance pathways.
The median PFS was 7.8 months for elacestrant plus ribociclib and 8.3 months for elacestrant plus everolimus in efficacy-evaluable patients with prior ET plus CDK4/6 inhibitor therapy. Elacestrant combinations with ribociclib or everolimus had safety profiles consistent with those of each drug when combined with SOC ET. Common and ≥Grade 3 treatment-emergent adverse events (TEAEs) for the recommended phase 2 dose of elacestrant plus ribociclib, and for the recommended phase 2 dose of elacestrant plus everolimus can be seen in the Table below. Most AEs were mild (grade 1-2), with manageable safety profiles. The recommended phase 2 doses were identified as elacestrant 345 mg plus ribociclib 400 mg daily, and elacestrant 345 mg plus everolimus 7.5 mg daily.
These findings support elacestrant as a potential ET backbone for use with various targeted agents, offering an all-oral treatment regimen that delays the need for chemotherapy- or antibody–drug conjugate-based regimens.
Source: Rugo H, et al. Elacestrant (Ela) combinations with ribociclib (Ribo) and everolimus (Eve) in patients (pts) with ER+/HER2- locally advanced or metastatic breast cancer (mBC): update from ELEVATE, a phase (Ph) 1b/2, open-label, umbrella study. Presented at: 2025 ASCO Annual Meeting. May 30-June 3, 2025; Chicago, IL. Abstract 1070.
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