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Olubukola Ayodele: Summary of the EMBER-3 trial

Olubukola Ayodele/LinkedIn

Dec 12, 2024, 13:36

Olubukola Ayodele: Summary of the EMBER-3 trial

Olubukola Ayodele, Consultant Medical Oncologist at the University Hospitals of Leicester NHS Trust, posted on LinkedIn:

“Summary of the EMBER-3 trial.

ESR1-mutation are enriched in metastatic breast cancer (MBC) following endocrine treatment especially after aromatase inhibitors (AI) exposure.

Imlunestrant is a next-generation, brain-penetrant, oral SERD and pure ER
antagonist that delivers continuous ER inhibition.

Who were the patients in EMBER-3?

Median age 62 years
1/3rd had adjuvant only treatment
2/3rd had 1st line prior treatment for MBC
Approximately 60% prior CDK4/6 inhibitors (mostly palbociclib or ribociclib).
None with prior PIK3CA or AKT targeted treatment.
Range of ESR1-mut 32-42%
40% with PIK3 pathway mutations

This is the first instance where oral SERDs appears to breakout from the ESR1-mut box perhaps reflecting a more active endocrine agent in combination with effective targeting of cross-talk pathways in tumours but fundamentally remain ER dependent.

Important to consider some design constraints:

Imlunestrant + abemaciclib lacks a standard control arm. They could have been fulvestrant + abemaciclib, fulvestrant + alpelisib or fulvestrant + capivasertib
Would the lack of exposure to CDK4/6 inhibitors in 40% of patients drive overall outcomes? I don’t think so as the forrest plot analysis showed that the patients with exposure to prior CDK4/6 inhibitors actually did better with HR 0.51 vs 0.82

EMBER-3 showed double mPFS benefit compared to all other randomised trials of prior CDK4/6 inhibitors.

Posthoc exploratory analysis showed decrease incidence rate of CNS progression. Trend towards OS benefit but too early to make any conclusions. No new safety signal observed and only 6% of discontinuity rate.

This is definitely going to become a new 2nd line treatment option for ER+ HER2 – MBC with FDA approval maybe in the new year.

All I can say is management of breast cancer is getting more complicated!!!”

Olubukola Ayodele: Summary of the EMBER-3 trial

Dr. Olubukola Ayodele is a Consultant Medical Oncologist at the University Hospitals of Leicester NHS Trust, specializing in breast and genitourinary malignancies, including germ cell tumors. She is also an honorary Senior Lecturer at the University of Leicester and heads the Breast Cancer Clinical Trials Unit at the Leicester Cancer Research Centre. Dr. Ayodele’s work includes numerous publications, clinical trials, and collaborative research projects on molecular drivers and biomarkers in breast cancer. She is a member of ASCO, ESMO, ACP and UKBCG.