I februariry 2023, the Food and Drug Administration (FDA) approved elacestrant (Orserdu, Stemline Therapeutics, Inc.) for women or men over 50 who have advanced or metastatic breast cancer and are ER-positive, HER2-negative, and have ESR1 mutations. The disease has progressed after at least one line of endocrine therapy.
Guardant360 CDx-analysen fick också FDA-godkännande som ett kompletterande diagnostiskt verktyg för elacestrantbehandling av patienter med bröstcancer.
EMERALD (NCT03778931), a randomised, open-label, active-controlled, multicenter trial that included 478 postmenopausal women and men with advanced or metastatic bröstcancer in whom 228 patients had ESR1 mutations, investigated the effectiveness of the treatment. Patients had to have seen disease progression after receiving one or more lines of endocrine therapy in the past, including at least one line that contained a CDK4/6 inhibitor. Patients who were eligible could have had up to one prior line of chemotherapy for advanced or metastatic disease. Elacestrant 345 mg orally once daily was given to patients who were randomly assigned (1:1) to receive it or investigator’s choice of endocrine therapy, which included fulvestrant (n=166) or an aromatase inhibitor (n=73). ESR1 mutation status (found vs. not found), previous fulvestrant treatment (yes vs. no), and visceral metastasis were used to divide the patients into groups for randomization (yes vs. no). The Guardant360 CDx assay was used to identify ESR1 missense mutations in the ligand binding domain and was limited to blood circulating tumour deoxyribonucleic acid (ctDNA).
The main efficacy outcome measure was progression-free survival (PFS), which underwent evaluation by a blinded imaging review committee. In the population with ITT and in the subgroup of patients with ESR1 mutations, there was a statistically significant difference in PFS.
Median-PFS var 3.8 månader (95 % KI: 2.2, 7.3) för de 228 (48 %) patienterna med ESR1-mutationer behandlade med elacestrant och 1.9 månader (95 % KI: 1.9, 2.1) för de som behandlades med fulvestrant eller en aromatashämmare (hazard ratio [HR] på 0.55 [95 % KI: 0.39, 0.77], 2-sidigt p-värde=0.0005).
De 250 (52 %) patienterna utan ESR1-mutationer i den explorativa analysen av PFS hade en HR på 0.86 (95 % CI: 0.63, 1.19) vilket tyder på att resultaten som sågs i ESR1-mutantpopulationen var övervägande ansvariga för förbättringen i ITT-kohorten .
Muskuloskeletal smärta, illamående, förhöjt kolesterol, förhöjt ASAT, förhöjda triglycerider, trötthet, minskat hemoglobin, kräkningar, förhöjt ALAT, förhöjt natrium, förhöjt kreatinin, minskad aptit, diarré, huvudvärk, förstoppning, buksmärtor, värmevallningar var, och frekventa biverkningar (10 %), inklusive laboratorieavvikelser.
Det rekommenderas att ta 345 mg elacestrant en gång dagligen med mat tills sjukdomen fortskrider eller toxiciteten blir outhärdlig.
View full prescribing information for Orserdu.
