The world’s first oral SERD has been approved, adding another member to the advanced breast cancer killer!

Breast cancer endocrine therapy is an important means of treatment of hormone receptor positive breast cancer. The main cause of drug resistance in HR+ patients after receiving first-line therapy (tamoxifen TAM or aromatase inhibitor AI) is mutations in the estrogen receptor gene α (ESR1). Patients receiving selective estrogen receptor degraders (SERDs) benefited regardless of ESR1 mutation status.

On January 27, 2023, the FDA approved elacestrant (Orserdu) for postmenopausal women or adult men with advanced or metastatic breast cancer with ER+, HER2-, ESR1 mutations and disease progression after at least one line of endocrine therapy. cancer patients. The FDA also approved the Guardant360 CDx assay as an adjunct diagnostic device to screen breast cancer patients receiving elastran.

This approval is based on the EMERALD (NCT03778931) trial, the main findings of which were published in the JCO.

The EMERALD study (NCT03778931) is a multi-center, randomized, open-label, active-controlled phase III clinical trial that enrolled a total of 478 postmenopausal women and men with ER+, HER2- advanced or metastatic disease, 228 of whom had ESR1 mutations . The trial required patients with disease progression after prior first-line or second-line endocrine therapy, including CDK4/6 inhibitors. Eligible patients had received at most first-line chemotherapy. Patients were randomized (1:1) to receive erastrol 345 mg orally once a day (n=239) or investigator’s choice of endocrine therapy (n=239), including fulvestrant (n=239). 166) or aromatase inhibitors (n=73). Trials were stratified according to ESR1 mutation status (detected vs. not detected), prior fulvestrant therapy (yes vs. no), and visceral metastases (yes vs. no). ESR1 mutation status was determined by ctDNA using the Guardant360 CDx assay and was restricted to ESR1 missense mutations in the ligand-binding domain.

The primary efficacy endpoint was progression-free survival (PFS). Statistically significant differences in PFS were observed in the intention-to-treat (ITT) population and subgroups of patients with ESR1 mutations.

Among 228 patients (48%) with an ESR1 mutation, median PFS was 3.8 months in the elacestrant group versus 1.9 months in the fulvestrant or aromatase inhibitor group (HR=0.55, 95% CI: 0.39-0.77, two-sided p-value = 0.0005).

An exploratory analysis of PFS in 250 (52%) patients without ESR1 mutations showed a HR of 0.86 (95% CI: 0.63-1.19), suggesting that the improvement in the ITT population was largely attributable to results in the ESR1 mutation population.

Most common adverse events (≥10%) included laboratory abnormalities including musculoskeletal pain, nausea, increased cholesterol, AST increased, triglycerides increased, fatigue, decreased hemoglobin, vomiting, ALT increased, sodium decreased , increased creatinine, decreased appetite, diarrhea, headache, constipation, abdominal pain, hot flashes, and indigestion.

The recommended dose of elastrol is 345 mg orally once daily with food until disease progression or unacceptable toxicity.

This is the first oral SERD drug to achieve positive top-line results in a pivotal clinical trial in patients with ER+/HER2- advanced or metastatic breast cancer. And regardless of the general population or the ESR1 mutation population, Erasetran brought statistically significant reductions in PFS and death risk, and showed good safety and tolerability.

Post time: Apr-23-2023