Elacestrant Shows Real-World Effectiveness in Metastatic Breast Cancers

Patients with ER-positive/HER2-negative metastatic breast cancer who received elacestrant experienced a significant reduction in disease progression or death compared with standard-of-care endocrine therapy. | Image Credit: Chinnapong - stock.adobe.com

Elacestrant was determined safe and effective following first line treatment for patients with ER-positive/HER2-negative advanced breast cancer, according to 2 posters presented at the San Antonio Breast Cancer Symposium 2024.^1,2

Progression-Free Survival Benefit

The first poster shows elacestrant displayed a consistent real-world progression-free survival (PFS) benefit among all patients with ER-positive/HER2-negative metastatic breast cancer and across clinically relevant subgroups.¹

The standard-of-care treatment for first line therapy of ER-positive/HER2-negative advanced or metastatic breast cancer is endocrine therapy combined with cyclin-dependent kinase (CDK) 4/6 inhibitors. Guidelines suggest sequential endocrine monotherapy or combination therapies used after first line treatment.

Patients with metastatic breast cancer who use combination therapies following second-line treatment can experience significant toxicities and high discontinuation rates. About 50% of patients who use first-line therapy will have ESR1 mutations following first-line treatment for ER-positive/HER2-negative metastatic breast cancer.

Elacestrant received FDA approval in January 2023 to treat patients with postmenopausal ER-positive/HER2-negative ESR1 mutated advanced or metastatic breast cancer with disease progression following at least 1 line of endocrine therapy. The approval was based on results from the EMERALD trial (NCT03778931), a randomized, open-label, multicenter study.³

Patients who received single-agent elacestrant had a 45% reduction in risk of progression or death compared with the standard-of-care endocrine therapy.¹ Elacestrant had a median PFS of 3.8 months while the standard-of-care endocrine therapy was 1.9 months (95% CI, 0.39-0.77; P = .0005).

The current study aimed to describe the real-world PFS of elacestrant while considering patients with no prior exposure to fulvestrant who only had 1 to 2 previous endocrine therapy treatments, 3 or more lines of endocrine therapy, and/or visceral metastasis.

Adults with ER-positive/HER2-negative metastatic breast cancer who initiated elacestrant in a real-world setting were enrolled between January 2023 through May 2024. There were 276 total patients, 106 of whom did not have any prior fulvestrant doses.

Elacestrant demonstrated consistent real-world PFS benefits across all patients and clinically relevant subgroups. The overall median PFS for patients with no prior fulvestrant (n = 106) was 9.4 months compared with the total population (n = 276) that reached PFS after 6.8 months.

Patients with no prior fulvestrant following 1 to 2 lines of endocrine therapy had a median PFS of 9.4 months while the total patient population reached 8 months. Visceral metastasis reached 6.1 months for the total patient population compared with 7.3 months for the subgroup.

The real-world differences between routine clinical care compared with prospective trials limit the study findings because they inpact multiple factors like treatment heterogeneity, tumor burden, genomic profile, and follow-up duration from the time of the initial elacestrant treatment.

Further research is necessary to discover variations of patient populations and baseline characteristics. Future analysis of coexisting mutations and other clinically relevant subgroups will provide meaningful insights to help inform real-world clinical decision-making.

The second poster focused on elacestrant combined with abemaciclib in patients with prior endocrine therapy combined with CDK4/6 inhibitors from the ongoing ELECTRA and ELEVATE studies.²

Tumors usually develop resistance following the first line of therapy due to the intrinsic alterations that emerge in up to 50% of patients. This can often lead to disease progression in patients.

The EMERALD trial led to the first oral selective estrogen receptor degrader approved in ER-positive/HER2-negative metastatic breast cancer. The drug targets ESR1-mutated tumors, reducing the overall risk of progression or death by 45% with elacestrant compared with standard-of-care therapy (95% CI, 0.39-0.77). Patients who received endocrine therapy for 12 months or more combined with CDK4/6 inhibitors and ESR1-mutated tumors had a median PFS of 8.6 months compared with 1.9 months with standard-of-care (95% CI, 0.26-0.63).

The pooled analysis reported new safety and preliminary efficacy for elacestrant combined with abemaciclib in combination with patients with prior endocrine therapy and CDK4/6 inhibitor exposure from both the ELECTRA (NCT05386108) and ELEVATE (NCT05563220) studies.

Participants (N = 42) were administered elacestrant 345 mg once a day combined with abemaciclib 150 mg twice daily. The population comprised all women, with 60 as the average age. Metastatic sites were mainly visceral (71%) with ESR1 mutations (53%).

The responses and clinical benefits patients (n = 38) had with elacestrant combined with abemaciclib were examined among efficacy-evaluable participants. Comparable safety and efficacy were evident in the complete response (5%), partial response (13%), stable disease (66%), and progressive disease (16%) rates.

Treatment-emergent adverse events (TEAEs) included diarrhea (83%), nausea (64%), vomiting (41%), fatigue (36%), neutropenia (33%), anemia (24%), constipation (21%), and decreased appetite (21%). All of the TEAEs were grade 3 or lower.

The median PFS was 8.7 months among all patients with ESR1-mutated tumors and 7.2 months in tumors with ESR1 mutations not detected. Patients who received prior endocrine therapy with CDK 4/6 inhibitors for 12 months or more had an average PFS of 16.6 months.

Patients with prior endocrine therapy combined with CDK4/6 inhibitors had consistent safety outcomes with elacestrant and abemaciclib therapy. Despite ESR1-mutation status, elacestrant combined with abemaciclib showed clinically meaningful efficacy rates.

“Endocrine resistance is very complicated. It includes several mechanisms. We try to combine these treatments to potentially work in different pathways and therefore overcome resistance that might emerge,” said Virginia Kaklamani, MD, DSc, contributing abstract study author and professor of medicine, Division of Hematology-Medical Oncology, University of Texas Health Science Center at San Antonio.

Future clinical trials can examine elacestrant in combination with abemaciclib in patients with ER-positive/HER2-negative metastatic breast cancer based on its potential to extend the PFS, enable an all-oral treatment option, and delay chemotherapy or antibody drug conjugate-based regimens.

References

1. Swallow E, Maitland J, Sarathy K, et al. Elacestrant real-world progression free survival of adult patients with ER+/HER2–, advanced breast cancer: a retrospective analysis using insurance claims in the United States. Presented at: San Antonio Breast Cancer Symposium 2024; December 10-13, 2024; San Antonio, Texas. Poster P3-10-08.

2. Rugo HS, Tolaney SM, Chan N, et al. Elacestrant plus abemaciclib combination in patients with estrogen receptor-positive (ER+), HER2– advanced or metastatic breast cancer. Presented at: San Antonio Breast Cancer Symposium 2024; December 10-13, 2024; San Antonio, Texas. Poster PS7-07.

3. Ryan C. FDA approves elacestrant for ER+/HER2–, ESR1-mutated advanced or metastatic breast cancer. AJMC^®. January 27, 2023. Accessed December 11, 2024. https://www.ajmc.com/view/fda-approves-elacestrant-for-er-her2-esr1-mutated-advanced-or-metastatic-breast-cancer