In Februariery 2023, die Food and Drug Administration (FDA) het elacestrant (Orserdu, Stemline Therapeutics, Inc.) goedgekeur vir vroue of mans ouer as 50 wat gevorderde of metastatiese borskanker het en ER-positief, HER2-negatief is en ESR1-mutasies het. Die siekte het gevorder na ten minste een lyn van endokriene terapie.
Die Guardant360 CDx-toets is ook deur die FDA goedgekeur as 'n metgeseldiagnostiese hulpmiddel vir elacestrant-behandeling van pasiënte met borskanker.
EMERALD (NCT03778931), a randomised, open-label, active-controlled, multicenter trial that included 478 postmenopausal women and men with advanced or metastatic borskanker 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).
Die belangrikste doeltreffendheid-uitkomsmaatstaf was progressievrye oorlewing (PFS), wat deur 'n verblinde beeldhersieningskomitee geëvalueer is. In die populasie met ITT en in die subgroep van pasiënte met ESR1 mutasies, was daar 'n statisties beduidende verskil in PFS.
Die mediaan PFS was 3.8 maande (95% KI: 2.2, 7.3) vir die 228 (48%) pasiënte met ESR1-mutasies wat met elacestrant behandel is en 1.9 maande (95% CI: 1.9, 2.1) vir diegene wat met fulvestrant of 'n aromatase-inhibeerder behandel is. (gevaarverhouding [HR] van 0.55 [95% CI: 0.39, 0.77], 2-sydige p-waarde=0.0005).
Die 250 (52%) pasiënte sonder ESR1-mutasies in die verkennende analise van PFS het 'n HR van 0.86 (95% CI: 0.63, 1.19) gehad wat aandui dat die resultate wat in die ESR1-mutantpopulasie gesien is, hoofsaaklik verantwoordelik was vir die verbetering in die ITT-kohort .
Muskuloskeletale pyn, naarheid, verhoogde cholesterol, verhoogde AST, verhoogde trigliseriede, moegheid, verlaagde hemoglobien, braking, verhoogde ALT, verhoogde natrium, verhoogde kreatinien, verminderde eetlus, diarree, hoofpyn, hardlywigheid, abdominale pyn, warm gloed was, en gereelde nadelige gebeurtenisse (10%), insluitend laboratoriumafwykings.
Dit word aangeraai om 345 mg elacestrant een keer per dag saam met kos te neem totdat die siekte vorder of die toksisiteit ondraaglik word.
View full prescribing information for Orserdu.
