Drugs Xagena
The US Food and Drug Administration (FDA) has approved Elacestrant ( Orserdu ) for the treatment of postmenopausal women or adult men with estrogen receptor–positive (ER+), human epidermal growth factor receptor 2–negative (HER2–), estrogen receptor 1 (ESR1)–mutated advanced or metastatic breast cancer with disease progression after at least one line of endocrine therapy (ET).
Approval was based on EMERALD, a randomized, open-label, active-controlled, multicenter trial in 478 patients with ER+, HER2– advanced or metastatic breast cancer, including 228 patients with ESR1 mutations. Patients were randomly assigned (1:1) to receive either Elacestrant 345 mg orally once daily (n = 239) or investigator's choice of endocrine therapy (n = 239).
In the ESR1-mut subgroup, EMERALD demonstrated a statistically significant improvement in progression-free survival (PFS) by blinded independent central review assessment (n = 228; hazard ratio [HR], 0.55 [95% CI, 0.39 to 0.77]; P value = 0.0005). Although the overall survival (OS) end point was not met, there was no trend toward a potential overall survival detriment (HR, 0.90 [95% CI, 0.63 to 1.30]) in the ESR1-mut subgroup. Progression-free survival also reached statistical significance in the intention-to-treat population (ITT, N = 478; HR, 0.70 [95% CI, 0.55 to 0.88]; P value = 0.0018). However, improvement in progression-free survival in the ITT population was primarily attributed to results from patients in the ESR1-mut.
The most common adverse events (greater than or equal to 10%), including laboratory abnormalities, were musculoskeletal pain, nausea, increased cholesterol, increased AST, increased triglycerides, fatigue, decreased hemoglobin, vomiting, increased ALT, decreased sodium, increased creatinine, decreased appetite, diarrhea, headache, constipation, abdominal pain, hot flush, and dyspepsia.
The recommended Elacestrant dose is 345 mg taken orally with food once daily until disease progression or unacceptable toxicity. ( Xagena )
Shah M et al, J Clin Oncol 2024;42(10):1193-1201
XagenaMedicine_2024
