KEY TAKEAWAYS
- The phase 3 EMERALD trial aimed to assess elacestrant’s effectiveness against standard therapy for ESR1-mutated metastatic breast cancer patients.
- Elacestrant’s efficacy increased with ≥12 months of prior CDK4/6i, indicating endocrine sensitivity.
- It still remains a preferable monotherapy for ER+ mutations despite resistance factors.
In the EMERALD trial, elacestrant showed a prolonged progression-free survival (PFS) and a manageable safety profile compared to standard endocrine therapy in patients with ER+/HER2− ESR1 mutated (ESR1-mut) metastatic breast cancer (mBC) after previous endocrine therapy. Notably, this trial is distinctive as it required prior CDK4/6 inhibitor use.
The duration of prior CDK4/6 inhibitor treatment was observed to predict the efficacy of elacestrant in patients with ESR1 mutations. Patients who received elacestrant after at least 12 months of CDK4/6 inhibitor treatment demonstrated a median PFS of 8.61 months compared to 1.91 months for standard therapy.
A. Bardia and a team of researchers assessed the clinical benefit of elacestrant in various subgroups, including those with biomarkers usually linked to poorer prognosis.
The patients with ER+/HER2- advanced or mBC who had undergone 1-2 lines of prior endocrine therapy along with prior CDK4/6 inhibitor treatment were divided equally to receive elacestrant or standard treatment (aromatase inhibitor or fulvestrant).
Researchers conducted a subgroup analysis that targeted patients with ESR1 mutations, evaluating their prior CDK4/6 inhibitor use lasting at least 12 months in the advanced or metastatic stage. They considered patients with liver and/or lung metastases, PIK3CA mutations, TP53 mutation, and low HER2 expression.
A total of 478 patients were involved in the study, evenly split between those receiving elacestrant (n=239) and standard treatment (n=239). Among these patients, 228 individuals (47.7%) had ESR1 mutations, with 159 of them (71.6%) having undergone at least 12 months of prior CDK4/6 inhibitor treatment. Within this subset, 113 patients (71%) had liver and/or lung metastases, 62 patients (39%) had a PIK3CA mutation, 61 patients (38%) had TP53 mutations, and 77 patients (48%) had low HER2 expression.
Notably, the study indicated that elacestrant displayed a meaningful improvement in progression-free survival (PFS) compared to standard treatment when patients had undergone CDK4/6 inhibitor treatment for at least 12 months, indicating its potential effectiveness for those responsive to endocrine therapy. Interestingly, elacestrant exhibited better outcomes compared to standard treatment, even among patients with additional challenges like PIK3CA or TP53 mutations, low HER2 expression, or liver/lung metastases.
These findings highlight the continued effectiveness of the estrogen receptor pathway, making oral elacestrant an appealing option for this group despite other potential resistance mechanisms. This suggests that elacestrant alone could be a viable alternative to combination therapies or HER2 low-targeted ADCs administered intravenously.
The study is sponsored by Stemline Therapeutics, Inc.
Source: https://atgproductions.net/atgclients/sabcs/2023_SABCS_Abstract_Report-12-1-23_Compressed.pdf
Clinical Trial: https://clinicaltrials.gov/study/NCT03778931
Bardia, A., O’Shaughnessy, J., Bidard, F. et al. (2023). “Elacestrant vs standard-of-care in ER+/HER2- advanced or metastatic breast cancer (mBC) with ESR1 mutation: key biomarkers and clinical subgroup analyses from the phase 3 EMERALD trial.” Presented at the SABCS 2023 – 46th Annual San Antonio Breast Cancer Symposium, December 05 – December 09, 2023, San Antonio, TX, US (Abstract PS17-02).
