Results of the EMERALD study: Prof François Duhoux meets Prof Janice Lu

Prof Janice Lu, Professor of Medicine at Northwestern University in Chicago and also Director of the Breast Medical Oncology Department at the Robert H. Lurie Comprehensive Cancer Center, discusses with Prof François Duhoux, medical oncologist and head of clinic of the department of oncology at the Cliniques Universitaires in Brussels, on a subgroup analysis of the EMERALD trial that was presented during a poster spotlight session at SABCS 2023.  

The EMERALD Study presented at San Antonio is a phase III registrational trial design. The study demonstrated a statistically significant improvement in median PFS with elacestrant compared to standard pure endocrine monotherapy in ER+/HER2- advanced or metastatic breast cancer harbouring ESR1-mutations. The FDA approved elacestrant in January 2023 for postmenopausal women or adult men with ER+/HER2- ESR1-mutation metastatic breast cancer. Notably, patients with prior CDK4/6 inhibitor therapy for at least 12 months achieved a median PFS of 8.6 months with elacestrant, indicating endocrine sensitivity. The drug, a single-agent oral therapy, offers a valuable option for delaying disease progression and potentially deferring the need for chemotherapy.

In the key updated findings presented at San Antonio, a subgroup analysis of endocrine-sensitive populations revealed favourable PFS outcomes across prevalent clinical and biomarker subgroups. Elacestrant demonstrated superiority over the standard of care in ESR1-mutant tumours, irrespective of metastatic site, coexisting mutations (e.g., PIK3CA or TP53), or HER2 expression. PFS ranged from 7.3 to 9.1 months for elacestrant, significantly longer than the 1.9 months observed with standard of care. The coexistence of ESR1 and PIK3CA mutations showed a progression-free survival of 5.5 months, suggesting the potential of elacestrant in addressing endocrine-sensitive disease with these co-mutations.

No new safety signals were reported compared to initial data. Elacestrant exhibited well-managed side effects, including muscle aches, fatigue, nausea, diarrhoea, and elevated liver functions. Future research directions include exploring elacestrant as a backbone for endocrine therapy in combination with other targeted therapies, as demonstrated by the ELEVATE and ELECTRA studies presented at San Antonio in 2023. These investigations aim to optimise elacestrant’s benefits and expand its applications in various treatment sequences and combinations, offering promising avenues for improving patient outcomes. The study emphasises the importance of testing for ESR1-mutations upon disease progression, particularly after prolonged CDK4/6 inhibitor therapy, to guide the application of elacestrant as a well-tolerated oral therapy.

Reference:

Bardia A.. et al., 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. SABCS 2023 # PS17-02