Noong Pebrerory 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.
Ang Guardant360 CDx assay ay binigyan din ng pag-apruba ng FDA bilang isang kasamang diagnostic tool para sa elacestrant na paggamot ng mga pasyenteng may kanser sa suso.
EMERALD (NCT03778931), a randomised, open-label, active-controlled, multicenter trial that included 478 postmenopausal women and men with advanced or metastatic dibdib kanser 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.
Ang median PFS ay 3.8 buwan (95% CI: 2.2, 7.3) para sa 228 (48%) na mga pasyente na may ESR1 mutations na ginagamot ng elacestrant at 1.9 na buwan (95% CI: 1.9, 2.1) para sa mga ginagamot sa fulvestrant o isang aromatase inhibitor (hazard ratio [HR] ng 0.55 [95% CI: 0.39, 0.77], 2-sided p-value=0.0005).
Ang 250 (52%) na mga pasyente na walang ESR1 mutations sa exploratory analysis ng PFS ay mayroong HR na 0.86 (95% CI: 0.63, 1.19) na nagpapahiwatig na ang mga resulta na nakikita sa ESR1 mutant na populasyon ay higit na responsable para sa pagpapabuti sa ITT cohort .
Sakit ng musculoskeletal, pagduduwal, mataas na kolesterol, mataas na AST, mataas na triglycerides, pagkapagod, pagbaba ng hemoglobin, pagsusuka, mataas na ALT, mataas na sodium, mataas na creatinine, pagbaba ng gana sa pagkain, pagtatae, sakit ng ulo, paninigas ng dumi, pananakit ng tiyan, hot flush, at dyspepsia ang karamihan. madalas na masamang kaganapan (10%), kabilang ang mga abnormalidad sa laboratoryo.
Pinapayuhan na uminom ng 345 mg ng elacestrant isang beses araw-araw kasama ng pagkain hanggang sa lumala ang sakit o ang toxicity ay hindi na matitiis.
View full prescribing information for Orserdu.
