The EMERALD trial is a phase III clinical trial which randomised patients with oestrogen receptor positive/HER2 negative metastatic breast cancer to receive either elacestrant or standard of care endocrine therapy, depending on the prior endocrine therapy that patients had received. All patients on the trial had received a prior CDK4/6 inhibitor in the metastatic setting. There were two primary endpoints of the study: the first was progression free survival in the whole patient population and the second one was progression free survival in the patient population with tumours that had ESR1 mutations.
What was the methodology of the study?
This was a randomised phase III clinical trial with two primary endpoints and it was a registrational trial.
What were the key findings?
The key findings of the trial were that elacestrant outperformed standard of care endocrine therapy in both primary endpoints – both in the median progression free survival and the median progression free survival in patients with tumours that had ESR1 mutations.
The follow-up data that was presented at the San Antonio Breast Cancer Symposium this year was that patients’ duration of elacestrant and standard of care therapy was dependent on prior duration of CDK4/6 inhibition. But the longer the CDK4/6 inhibition duration was, the longer the elacestrant duration was as well. The difference between the elacestrant and the standard of care arm was increased by the longer duration of a CDK4/6 inhibitor.
What do you think will be the clinical impact of these results and what is the future for this study?
The clinical impact of the results that we presented is pretty big. We know that patients that initially received the CDK4/6 inhibitor and endocrine therapy in the metastatic setting, their tumours start becoming endocrine resistant. So after the progression on a CDK4/6 inhibitor we struggle a lot of times with what treatment to give next. We can give combination endocrine therapy, we can give chemotherapy, but both of these options have quite a bit of toxicity.
The EMERALD trial showed that if we have a tumour that is endocrine sensitive, and the way we gauge that is by duration of the prior CDK4/6 inhibitor, that there is a very good option in giving patients elacestrant, especially in the patients whose tumours are ESR1 mutated. Those patients can take single agent endocrine therapy with a very manageable side effect profile instead of getting either combination therapy or jumping to chemotherapy.
Elacestrant is currently being evaluated by the FDA for approval and obviously, depending on how this approval goes through, this will be a way to use elacestrant in clinical care.