SERD yapakamwa yoyamba padziko lonse lapansi yavomerezedwa, ndikuwonjezera membala wina kwa wakupha khansa ya m'mawere wapamwamba!

Chithandizo cha khansa ya m'mawere endocrine ndi njira yofunikira yochizira khansa ya m'mawere yolandira ma hormone.Chifukwa chachikulu cha kukana mankhwala kwa odwala HR + atalandira chithandizo choyamba (tamoxifen TAM kapena aromatase inhibitor AI) ndi kusintha kwa estrogen receptor gene α (ESR1).Odwala omwe amalandila ma estrogen receptor degraders (SERDs) amapindula mosasamala kanthu za kusintha kwa ESR1.

Pa Januware 27, 2023, a FDA adavomereza elacestrant (Orserdu) kwa amayi omwe adasiya kusamba kapena amuna akuluakulu omwe ali ndi khansa ya m'mawere yapamwamba kapena metastatic ndi ER+, HER2-, ESR1 masinthidwe ndi kupitilira kwa matenda pambuyo pa mzere umodzi wamankhwala a endocrine.odwala khansa.A FDA adavomerezanso kuyesa kwa Guardant360 CDx ngati njira yodziwira odwala omwe ali ndi khansa ya m'mawere omwe amalandira elastran.

Chivomerezochi chimachokera ku mayesero a EMERALD (NCT03778931), zomwe anapeza zomwe zidasindikizidwa mu JCO.

Kafukufuku wa EMERALD (NCT03778931) ndi mayeso achipatala apakati, osasinthika, otseguka, oyendetsedwa mwachangu ndi gawo III omwe adalembetsa azimayi ndi abambo 478 omwe ali ndi ER+, HER2- advanced kapena metastatic matenda, 228 omwe anali ndi ESR1. masinthidwe .Mlanduwo unkafuna odwala omwe ali ndi matenda opitilira muyeso pambuyo pa mzere woyamba kapena wachiwiri wamankhwala a endocrine, kuphatikiza ma CDK4/6 inhibitors.Odwala oyenerera adalandira chithandizo chamankhwala choyambirira kwambiri.Odwala anali osankhidwa mwachisawawa (1: 1) kuti alandire erastrol 345 mg pakamwa kamodzi patsiku (n = 239) kapena kusankha kwa wofufuza wa endocrine therapy (n = 239), kuphatikizapo fulvestrant (n = 239).166) kapena aromatase inhibitors (n=73).Mayesero adasinthidwa malinga ndi kusintha kwa ESR1 (kuzindikiridwa vs. sikunazindikirike), chithandizo cham'mbuyo cha fulvestrant (inde vs. ayi), ndi visceral metastases (inde vs. ayi).Kusintha kwa ESR1 kudatsimikiziridwa ndi ctDNA pogwiritsa ntchito Guardant360 CDx assay ndipo idangoperekedwa ku ESR1 missense masinthidwe mu ligand-binding domain.

Chomaliza chothandiza chinali kupulumuka kwaulere (PFS).Kusiyana kwakukulu mu PFS kunawonedwa mu chiwerengero cha cholinga-to-treat (ITT) ndi magulu a odwala omwe ali ndi kusintha kwa ESR1.

Pakati pa odwala 228 (48%) omwe ali ndi kusintha kwa ESR1, PFS yapakati inali miyezi 3.8 mu gulu la elacestrant motsutsana ndi miyezi 1.9 mu gulu la fulvestrant kapena aromatase inhibitor (HR = 0.55, 95% CI: 0.39-0.77, p-value yamagulu awiri) = 0.0005).

Kufufuza kofufuza kwa PFS mwa odwala 250 (52%) opanda kusintha kwa ESR1 kunasonyeza HR ya 0.86 (95% CI: 0.63-1.19), kutanthauza kuti kusintha kwa chiwerengero cha ITT kunali makamaka chifukwa cha zotsatira za kusintha kwa ESR1.

Zoyipa zodziwika bwino (≥10%) zimaphatikizapo kuphwanya kwa labotale, kuphatikiza kupweteka kwa minofu ndi mafupa, nseru, kuchuluka kwa cholesterol, AST, kuchuluka kwa triglycerides, kutopa, kuchepa kwa hemoglobin, kusanza, kuchepa kwa ALT, kuchepa kwa sodium, kuchuluka kwa creatinine, kuchepa kwa chidwi, kutsekula m'mimba, kupweteka mutu, kudzimbidwa, kupweteka m'mimba, kutentha thupi, ndi kusadya bwino.

Mlingo woyenera wa elastrol ndi 345 mg pakamwa kamodzi tsiku lililonse ndi chakudya mpaka kukula kwa matenda kapena kawopsedwe kosavomerezeka.

Awa ndi mankhwala oyamba a pakamwa a SERD kuti akwaniritse zotsatira zabwino kwambiri pamayesero ofunikira azachipatala kwa odwala omwe ali ndi khansa ya m'mawere ya ER+/HER2- advanced kapena metastatic.Ndipo mosasamala kanthu za kuchuluka kwa anthu kapena kuchuluka kwa kusintha kwa ESR1, Erasetran inabweretsa kuchepetsedwa kwakukulu kwa PFS ndi chiopsezo cha imfa, ndipo inasonyeza chitetezo chabwino ndi kulolera.