Elacestrant (Orserdu) combined with abemaciclib (Verzenio) has shown clinical benefit and was well-tolerated in patients with estrogen receptor (ER)-positive, HER2-negative metastatic breast cancer, according to data from the phase 1b/2 ELECTRA trial (NCT05386108) presented at the 2024 ESMO Congress. These patients had previously been treated with endocrine therapy and another CDK4/6 inhibitor. The findings suggest a potential new treatment option for this heavily pretreated population.
ELECTRA Trial Details
The phase 1b portion of the ELECTRA trial enrolled patients aged 18 years or older with confirmed ER-positive, HER2-negative advanced or metastatic breast cancer. Key inclusion criteria included prior treatment with at least one line of endocrine therapy and no more than two lines of chemotherapy in the metastatic setting. Patients could not have received prior treatment with abemaciclib, elacestrant, or investigational selective estrogen receptor degraders. The primary endpoint of phase 1b was to determine the recommended phase 2 dose (RP2D).
Patients were assigned to one of three treatment cohorts: cohort 1 (elacestrant 258 mg daily plus abemaciclib 100 mg twice daily), cohort 2 (elacestrant 345 mg daily plus abemaciclib 100 mg twice daily), and cohort 3 (elacestrant 345 mg daily plus abemaciclib 150 mg twice daily). The RP2D was determined to be elacestrant 345 mg daily plus abemaciclib 150 mg twice daily.
Efficacy Outcomes
Evaluable patients treated across the three cohorts in phase 1b (n = 23) experienced an objective response rate (ORR) of 26%, which included one complete response (CR) and five partial responses (PRs). The clinical benefit rate (CBR) at 16 weeks and 24 weeks was 70% and 57%, respectively. Specifically, in cohort 3, which received the RP2D, the ORR was 25%, including 1 CR and 2 PRs, with 58% of patients achieving stable disease (SD) and a CBR at 16 weeks of 75%.
Safety Profile
The combination was generally well-tolerated. No grade 4 adverse effects (AEs) were reported, and no grade 3 diarrhea was observed. Neutropenia was mainly attributed to abemaciclib. Any-grade treatment-emergent adverse effects (TEAEs) were observed in 60% of patients in cohort 1 (n = 5), 86% of patients in cohort 2 (n = 7), and 92% in cohort 3 (n = 12). The most common any-grade TEAEs included diarrhea, nausea, neutropenia/decreased neutrophil count, and asthenia.
Expert Commentary
According to lead study author Eva M. Ciruelos, MD, PhD, of Hospital Universitario 12 de Octubre in Madrid, Spain, the combination was well tolerated and consistent with the known safety profile of abemaciclib and standard endocrine therapy. These early results suggest that the combination of elacestrant and abemaciclib may provide a valuable option for patients with pretreated ER-positive, HER2-negative metastatic breast cancer. The phase 2 portion of the trial will further evaluate the efficacy of this combination in patients with brain metastases.
