Elacestrant Combination Therapy Shows Promising Progression-Free Survival Results in ER+ Metastatic Breast Cancer
核心洞察
The Menarini Group (搜索) presented Phase 2 ELEVATE study data showing elacestrant combined with everolimus or abemaciclib demonstrated meaningful progression-free survival benefits in ER+/HER2 (搜索)- metastatic breast cancer (搜索) patients.
Elacestrant plus abemaciclib achieved a median progression-free survival of 14.3 months compared to 8.3 months for elacestrant plus everolimus across all patient populations.
The combination therapies showed consistent PFS benefits regardless of ESR1 (搜索) mutation status, with safety profiles consistent with known profiles of each individual drug.
The Menarini Group (搜索) and its subsidiary Stemline Therapeutics (搜索) presented encouraging Phase 2 data from the ELEVATE study at the 2025 San Antonio Breast Cancer Symposium, demonstrating that elacestrant in combination with either everolimus or abemaciclib shows meaningful progression-free survival benefits in patients with estrogen receptor (搜索)-positive (ER+), HER2 (搜索)-negative metastatic breast cancer (搜索).
ELEVATE Study Results Show Significant PFS Improvements
The Phase 2 ELEVATE study evaluated oral-oral combination treatment options designed to overcome different resistance mechanisms observed in ER+/HER2 (搜索)- metastatic breast cancer (搜索). The data presented at SABCS showed that elacestrant combined with abemaciclib achieved a median progression-free survival of 14.3 months [95% CI: 7.3-16.6] compared to 8.3 months [95% CI: 4.0-10.2] when combined with everolimus across all patients.
"The encouraging progression-free survival data increase our confidence in the role elacestrant could play as an endocrine therapy backbone in the combination setting," said Virginia Kaklamani, MD, DSc, Professor of Medicine in the Division of Hematology/Oncology at UT Health San Antonio, and Leader of the Breast Cancer Program at UT Health San Antonio MD Anderson Cancer Center.
The study enrolled patients who experienced disease progression on endocrine therapy, with or without prior exposure to CDK4/6 (搜索) inhibitors. Results showed consistent PFS benefits irrespective of ESR1 (搜索) mutation status, with the elacestrant plus abemaciclib combination demonstrating particularly robust efficacy across multiple patient subgroups.
Subgroup Analysis Reveals Broad Efficacy
In patients with visceral disease, elacestrant plus abemaciclib achieved a median PFS of 14.3 months [95% CI: 7.4-16.6] compared to 7.7 months [95% CI: 3.8-9.4] for the everolimus combination. Among patients with no prior fulvestrant exposure, the abemaciclib combination reached 14.8 months [95% CI: 8.7-NR] versus 8.3 months [95% CI: 4.2-12.9] for the everolimus combination.
For patients without primary endocrine resistance, median PFS was 14.3 months [95% CI: 7.3-16.6] with abemaciclib and 8.3 months [95% CI: 4.0-12.9] with everolimus. The study also evaluated genomic subgroups, with ESR1 (搜索)-mutated patients showing a median PFS of 8.7 months [95% CI: 3.5-12.9] in the everolimus arm, while maturity was not reached for the abemaciclib combination.
Safety Profile Remains Manageable
The safety analysis revealed that both combination regimens maintained safety profiles consistent with the known profiles of each individual targeted therapy plus standard endocrine therapy. "The safety profile of elacestrant in combination with everolimus or abemaciclib is consistent with the known safety profiles of each drug. No new safety signals have been observed," noted Dr. Kaklamani.
Extensive Clinical Development Program
The ELEVATE study represents one component of an expansive elacestrant clinical development program spanning both metastatic and early-stage breast cancer. Additional presentations at SABCS included data from the SOLTI-2104-PremièRe trial evaluating elacestrant in premenopausal women with early breast cancer (搜索), and the ELEGANT Phase 3 study comparing elacestrant versus standard endocrine therapy in node-positive, early breast cancer patients with high risk of recurrence.
"The extensive evidence for elacestrant spans the monotherapy setting in our pivotal EMERALD study, now backed by two recent real-world data publications, and in its growing potential in combination regimens, as highlighted by the data presented at SABCS," said Elcin Barker Ergun, CEO of the Menarini Group (搜索).
Ongoing Trials Expand Treatment Landscape
Several ongoing trials are further investigating elacestrant's potential across the breast cancer spectrum. The Phase 3 ADELA study is evaluating elacestrant plus everolimus versus elacestrant plus placebo in ER+/HER2 (搜索)- advanced breast cancer patients with ESR1 (搜索)-mutated tumors progressing on endocrine therapy plus CDK4/6 (搜索) inhibitors. The ERADICATE study is examining elacestrant plus trastuzumab deruxtecan in CDK4/6 inhibitor and endocrine-resistant HR+/HER2-low or HER2-ultralow metastatic breast cancer (搜索).
The ELEVATE trial (NCT05563220) is a phase 1b/2 clinical trial evaluating elacestrant combined with multiple targeted therapies including alpelisib, everolimus, capivasertib, palbociclib, ribociclib, and abemaciclib. Additional company-sponsored trials include ELECTRA (NCT05386108), which evaluates elacestrant in combination with abemaciclib in patients with brain metastases, and ELCIN (NCT05596409), assessing efficacy in patients who received prior hormonal therapies without CDK4/6 (搜索) inhibitors in the metastatic setting.