A recent post-hoc subgroup analysis of the Phase III EMERALD trial, presented at SABCS 2023 and published in Clinical Cancer Research, has shed light on the efficacy of elacestrant in treating ER+, HER2- metastatic breast cancer (MBC) patients harboring ESR1 mutations. The analysis focused on patients who had received CDK4/6 inhibitor plus endocrine therapy for a minimum of 12 months, examining outcomes across clinically relevant subgroups.
The EMERALD trial investigated elacestrant, a selective estrogen receptor degrader (SERD), in patients with ER+, HER2- MBC who had progressed on prior endocrine therapy. The subgroup analysis specifically assessed the drug's performance in patients with ESR1-mutated tumors, a population known to exhibit endocrine resistance.
The results indicated that elacestrant demonstrated clinical benefit in this subgroup, suggesting its potential as a valuable treatment option after progression on CDK4/6 inhibitor-based regimens. The study, led by Aditya Bardia et al., highlighted the importance of considering ESR1 mutation status when selecting therapies for ER+, HER2- MBC.
Clinical Implications
The findings from this EMERALD subgroup analysis have direct implications for clinical practice. Oncologists can now consider elacestrant as a viable option for patients with endocrine-sensitive, ESR1-mutated MBC, particularly those who have experienced disease progression on prior CDK4/6 inhibitor and endocrine therapy combinations. The data suggest that elacestrant can overcome some of the resistance mechanisms conferred by ESR1 mutations.
Study Details
The EMERALD trial was a randomized, open-label, Phase III study that compared elacestrant to standard endocrine therapy in patients with ER+, HER2- MBC. Patients were stratified based on ESR1 mutation status. The primary endpoint was progression-free survival (PFS) in the overall population and in the ESR1-mutated subgroup. Secondary endpoints included overall survival (OS), objective response rate (ORR), and safety.
The subgroup analysis further dissected the data based on prior duration of endocrine therapy plus CDK4/6 inhibitor and in various clinical subgroups, providing a more granular understanding of elacestrant's efficacy profile.
