At the 2022 San Antonio Breast Cancer Symposium, Aditya Bardia, MD, Massachusetts General Hospital, Boston, Massachusetts, presented updated results from the EMERALD trial, examining the efficacy of elacestrant vs standard of care endocrine therapy for patients with ER-positive, HER2-negative, metastatic breast cancer by duration of prior CDK4/6 inhibitors in metastatic setting.

Dr Bardia stated that patients with a longer duration of prior CDK4/6 inhibitors, representing endocrine-sensitive disease, were more likely to have a longer progression-free survival with elacestrant. Therefore, duration of prior CDK4/6 inhibitor may be able to serve as a surrogate marker to select for patients needing single agent endocrine therapy.

Transcript

I am Aditya Bardia, breast medical oncologist at Mass General Cancer Center, Harvard Medical School, Boston. The EMERALD trial was a clinical trial that evaluated a novel, oral selective estrogen receptor degrader, elacestrant, versus standard endocrine therapy for patients with metastatic hormone receptor-positive breast cancer in the second-line and plus setting. In this setting we tend to use fulvestrant as the standard endocrine therapy, but it's given as an intramuscular shot and the median [progression-free survival] PFS is low, usually around 2 months. There has been need for better endocrine agents in this setting. Elacestrant was evaluated in the global phase 3 clinical trial, EMERALD, comparing it to standard endocrine therapy, with most of these patients receiving fulvestrant. We saw the first results of the EMERALD trial at SABCS 2021 where patients who received elacestrant had better progression-free survival as compared to standard endocrine therapy.

At SABCS 2022, we see the updated results. The reason for the updated results is if we look at the PFS curves, we see that there's an initial drop in the curves and then separation. The initial drop is likely because of endocrine-resistant disease. Clinically there's been a question: Can we identify endocrine-sensitive disease? That's where you really see benefit with a novel endocrine agent, because these are ER-dependent tumors. We looked at prior duration of CDK4/6 inhibitor as a surrogate for endocrine-sensitive disease, and we found that the prior duration of CDK4/6 inhibitor kind of predicted for median PFS with elacestrant.

Patients who had longer duration of prior CDK4/6 were much more likely to have a longer duration with elacestrant. For example, for patients who had received prior CDK4/6 inhibitor duration of at least 12 months, the median PFS with elacestrant was more than 8 months versus about 2 months with fulvestrant in the estrogen receptor 1 mutant group. You could clearly see a separation in the curve that was clinically meaningful and statistically significant.

Overall, this provides 1 surrogate marker that can kind of predict for endocrine-sensitive disease for patients with hormone receptor-positive metastatic breast cancer, which could guide who needs single agent endocrine therapy.

Moving forward, there is also interest in combination therapy. There's a planned study looking at elacestrant with other agents such as PI3 kinase inhibitor, M2 inhibitors, and CDK4/6 inhibitors to further improve outcomes for patients with hormone receptor positive metastatic breast cancer.

Source:

Bardia A, Bidard FC, Neven P, et al. “EMERALD phase 3 trial of elacestrant versus standard of care endocrine therapy in patients with ER+/HER2- metastatic breast cancer: Updated results by duration of prior CDK4/6i in metastatic setting.” Presented at San Antonio Breast Cancer Symposium; December 6-10, 2022; San Antonio, Texas. Abstract GS3-01