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Phase 3 EMBER-3 trial results demonstrate significant progress in breast cancer treatment options, particularly for patients with ESR1 mutations. The study evaluated imlunestrant both as monotherapy and in combination with abemaciclib for patients with estrogen receptor-positive, HER2-negative advanced breast cancer who received prior endocrine therapy. The trial’s complex statistical design yielded multiple significant findings that could influence treatment protocols.
Key Points:
- Imlunestrant monotherapy showed superior progression-free survival in patients with ESR1 mutations (5.5 months vs 3.8 months with standard-of-care endocrine therapy; HR 0.62), including benefits across subgroups with visceral metastasis and prior CDK4/6 inhibitor use
- In the all-comers group, imlunestrant demonstrated minimal improvement in progression-free survival (5.6 months vs 5.5 months; HR 0.87), failing to meet the prespecified statistical significance threshold of 0.84
- The combination of imlunestrant plus abemaciclib significantly extended median progression-free survival to 9.4 months compared to 5.5 months with imlunestrant alone (HR 0.57)
- Safety profile analysis revealed fewer gastrointestinal side effects with imlunestrant compared to other oral SERDs, with notably absent class-specific adverse events such as bradycardia and photopsia
- Early data suggested potential central nervous system activity with the combination regimen, though this finding remains exploratory
- The study specifically examined second-line treatment following progression on first-line aromatase inhibitor with or without CDK4/6 inhibitor, with no prior endocrine therapy or chemotherapy allowed
“The second-line endocrine therapy space in metastatic disease is just becoming incredibly complex. It is wonderful to see all of these exciting data and these combinations that are having positive trial results.”
– Dr. Erin Frances Cobain, Associate Professor of Medicine, University of Michigan
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