Oral SERDs in ER+/HER2– mBC: Current Data and Future Directions

Comparative Study Analysis and CDK4/6 Inhibitor Sequencing

The EMBER-3 study compared single-agent imlunestrant, standard endocrine therapy, and imlunestrant combined with abemaciclib in a 3-arm design. Single-agent imlunestrant showed benefit only in patients who are ESR1 positive, consistent with other trials, while showing no improvement in the overall intention-to-treat population. The combination of imlunestrant plus abemaciclib demonstrated activity regardless of ESR1 status, supporting CDK4/6 inhibitor sequencing strategies.

Cross-trial comparisons between EMBER-3 [study] and EMERALD [study of elacestrant] are inappropriate due to fundamental population differences. EMBER-3 enrolled a less heavily pretreated population, with one-third receiving first-line therapy and none receiving third-line treatment, contrasting with EMERALD’s heavily pretreated cohort, where half received third-line therapy. Additional differences include prior chemotherapy exposure and fulvestrant use patterns.

Patient selection criteria significantly differed between studies, with EMERALD enrolling patients with higher rates of endocrine resistance and visceral crisis compared to EMBER-3. These population differences explain apparent efficacy variations between studies and emphasize the importance of appropriate patient selection. The studies address different clinical questions and patient populations rather than representing competing approaches.