The SERD elacestrant improves outcomes for patients unresponsive to endocrine therapy

According to the first results of the EMERALD trial, elacestrant shows clinical benefit over standard endocrine therapy in patients with oestrogen receptor (ER)-positive/HER2-negative metastatic breast cancer who progress on CDK4/6 inhibitor plus endocrine therapy.

At the moment, endocrine therapy plus CDK4/6 inhibitor is the mainstay for the management of ER-positive/HER2-negative metastatic breast cancer. However, most patients eventually experience disease progression, including development of ESR1 mutations (mESR1). Elacestrant, an oral selective oestrogen receptor degrader (SERD), demonstrated preclinical and clinical activity in a phase 1 trial in ER-positive metastatic breast cancer, including responses in patients with prior fulvestrant, CDK4/6 inhibitor, and mESR1 tumours, thus forming the rationale for the phase 3 EMERALD trial (NCT03778931) [1].

EMERALD enrolled 477 postmenopausal patients (228 with mESR1) with ER-positive/HER2-negative metastatic breast cancer who had received 1–2 prior lines of endocrine therapy and ≤1 line of chemotherapy in the metastatic setting, and who had prior progression on endocrine therapy plus a CDK4/6 inhibitor. Patients were randomised 1:1 to elacestrant (400 mg orally daily) or standard of care (investigator’s choice of fulvestrant or an aromatase inhibitor). Dr Aditya Bardia (Massachusetts General Hospital, MA, USA) presented the results [2].

A 30% reduction in the risk of progression in the elacestrant arm in all patients was measured (HR=0.697; P=0.0018) and a 45% reduction in the risk of progression in patients with mESR1 (HR=0.546; P=0.0005; see Figure). Progression-free survival rate at 12 months was 22.3% with elacestrant versus 9.4% with standard of care in all patients and 26.8% versus 8.2% in the mESR1 subgroup. For both endpoints, results in key prespecified subgroups –including visceral metastases, number of prior lines of therapy, and pre-treatment with fulvestrant– were consistent with the overall outcome. The prespecified interim overall survival analysis planned at the time of the final progression-free survival analysis demonstrated a trend in favour of elacestrant in all patients and in patients with mERS1 (HR=0.751 and 0.592, respectively).

Figure: Probability of progression-free survival for elacestrant versus standard of care in patients with ESR1-mutatedtumours [2].



 

 

 

 

 

PFS, progression-free survival; SOC, standard of care.

“Elacestrant is the first oral selective oestrogen receptor degrader to demonstrate a statistically significant and clinically meaningful improvement of progression-free survival in patients with ER-positive/HER2-negative metastatic breast cancer in the second-line and third-line settings, including for patients whose tumours harbour ESR1 mutations,” said Dr Bardia.

1. Bardia A, et al. J Clin Oncol 2021;39:1360–1370.
2. Bardia A, et al. Elacestrant, an oral selective estrogen receptor degrader (SERD), vs investigator’s choice of endocrine monotherapy for ER+/HER2- advanced/metastatic breast cancer (mBC) following progression on prior endocrine and CDK4/6 inhibitor therapy: Results of EMERALD phase 3 trial. GS2-02, SABCS 2021 Virtual Meeting, 7–10 December.

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Posted on 31 January, 2022