Positive EMERALD trial results for elacestrant to treat ER+/HER2- advanced breast cancer.

The data was presented as a “Late Breaker” and shared in an oral presentation by Dr. Aditya Bardia, MD.

The EMERALD trial (NCT03778931), a multicenter, international, randomized, open-label, controlled phase III trial evaluated elacestrant as a monotherapy versus SoC for the treatment of ER+/HER2- advanced or mBC. The trial enrolled patients who had received 1 or 2 prior lines of endocrine therapy (ET). Prior progression on an ET plus CDK4/6 : progression-free survival in the overall population and PFS in patients with tumors harboring Estrogen Receptor 1 mutations.

Trial Results: All patients were mandated to be treated with CDK 4/6 inhibitors. Moreover, patient population characteristics showed that 69.4% of patients had visceral metastasis and 22.2% received chemotherapy. EMERALD met both primary endpoints, which measured PFS of elacestrant as a monotherapy vs. SoC in the overall and mESR1 populations: Overall Population : i. Reduced risk of progression or death vs. SoC by 30% (HR=0.697 [95% CI: 0.552, 0.880]; P=0.0018) ii. Extended median PFS by 2.79 months versus SoC of 1.91. iii. At 12 months, probability of PFS was 22.3% (95% CI: 15.2%, 29.4%) with elacestrant vs. 9.4% (95% CI: 4.0%, 14.8%) with SoC. Compared to fulvestrant, elacestrant reduced risk of progression or death by 32% (HR=0.684 [95% CI: 0.521, 0.897]; P=0.0049).

ESR1 Mutation Population: i. Reduced risk of progression or death versus SoC by 45% (HR=0.546 [95% CI: 0.387, 0.768]; P=0.0005) ii. Extended median PFS by 3.78 months versus SoC of 1.87. iii At 12 months, probability of PFS was 26.8% (95% CI: 16.2%, 37.4%) with elacestrant vs. 8.2% (95% CI: 1.3%, 15.1%) with SoC. Compared to fulvestrant, elacestrant reduced the risk of progression or death by 50% (HR=0.504 [95% CI: 0.341, 0.741]; P=0.0005).

In both patient populations, results in key pre-specified subgroups, including visceral metastases, number of prior lines, and geographical region, were consistent with the overall outcome A key secondary endpoint for the EMERALD trial is Overall Survival (OS). A pre specified interim analysis indicates a trend favoring elacestrant over SoC in both patient groups. Final analysis is expected to occur in late 2022 or early 2023.

Safety Results: Elacestrant was well tolerated with an encouraging safety profile consistent with other ETs: TEAEs leading to discontinuation: infrequent in both elacestrant and SoC arms (6.3% and 4.4%). Grade 3 and higher TRAE were 7.2% for elacestrant and 3.1% for SoC. Grade 3 and higher adverse events for elacestrant: nausea, vomiting and diarrhea were 2.5%, 0.8% and 0%, respectively. A detailed evaluation of data is ongoing and additional results are expected to be published in a peer-reviewed journal.

Menarini plans to pursue combination studies and initiate activity in new lines of therapy such as the adjuvant setting, enabling elacestrant to be utilized in fully addressing the highest unmet needs for ER+/HER2-patients. In 2018, elacestrant received fast track designation from the FDA.