Giredestrant Neoadjuvant Kev Kho Mob Ntawm ER+/HER2- Thaum Ntxov Menopausal Cancer Yog Qhov Tseem Ceeb

Roche tsis ntev los no tshaj tawm cov ntaub ntawv ib ntus ntawm randomized Theem 2 coopERA kuaj mob qog noj ntshav ntawm lub 2021 European Society of Medical Oncology (ESMO) lub rooj sib tham virtual. Kev sim tshuaj ntsuam xyuas cov tiam tom ntej ntawm qhov ncauj xaiv estrogen receptor degrading agent (SERD) giredestrant (yav tas los hu ua GDC-9545) neoadjuvant kev kho mob ntawm ER-positive, HER2-negative postmenopausal ntxov cancer mis (eBC) cov neeg mob.

Cov txiaj ntsig tau pom tias nyob rau hauv lub qhov rais ntawm lub sijhawm tom qab 14 hnub ntawm kev kho mob, piv nrog anastrozole, kev kho mob giredestrant pom qhov txo qis hauv Ki67 (tus cim prognostic uas ntsuas cov qog proliferation) (feem ntau: 80% vs 67%, p=0.0222). Kev nyab xeeb ntawm giredestrant yog ua raws li cov kev sim yav dhau los, thiab cov neeg mob tsawg dua muaj kev phiv cuam tshuam txog giredestrant thiab anastrozole.

Roche Tus Thawj Saib Xyuas Kev Kho Mob thiab Tus Thawj Coj ntawm Kev Txhim Kho Cov Khoom Ntiaj Teb Levi Garraway, MD, tau hais tias:" Peb zoo siab heev los qhia rau koj txog thawj theem 2 cov ntaub ntawv ntawm Giredestrant, uas qhia tau hais tias Giredestrant yog qhov nthuav heev hauv HR- Cov neeg mob cancer mis zoo thiab HER2-negative. Txhawb kev ua si thiab kev nyab xeeb. Peb qhov kev txuas ntxiv ntawm HR-zoo mob qog noj ntshav lub mis muaj lub hom phiaj los hais txog cov kev xav tau tseem ceeb ntawm cov neeg mob uas tseem muaj kev cuam tshuam loj heev rau lawv lub neej zoo, suav nrog tshuaj tiv thaiv thiab kev pheej hmoo ntawm cov kab mob rov qab."

gredestrant chemical qauv

Giredestrant yog qhov ncauj, tiam tshiab SERD tsim los thaiv tag nrho ER teeb liab. Cov tshuaj muaj ib tug muaj zog receptor nyob (Receptor Occupancy) thiab qhia tshwj xeeb preclinical yam ntxwv. Estrogen txhawb txoj kev loj hlob ntawm HR-zoo mob qog noj ntshav mis los ntawm kev txuas mus rau ER. Giredestrant thaiv cov receptor no los tiv thaiv cov teebmeem ntawm estrogen, thiab hauv cov txheej txheem ua rau cov receptor degrade. Hauv kev sim tshuaj, giredestrant tau pom tias muaj txiaj ntsig tsis hais txog ESR1 kev hloov pauv (ESR1 noob hloov yog ib qho tseem ceeb ntawm kev kho cov tshuaj hormones).

Thaum Lub Kaum Ob Hlis 2020, US FDA tau tso cai giredestrant Fast Track Qualification (FTD) rau kev kho mob ntawm ER-positive, HER2-negative, thib ob-kab thiab thib peb-kab mob qog noj ntshav mis metastatic. giredestrant yog tswj hwm qhov ncauj thiab muaj kev txhawb nqa kev kho mob thiab kev nyab xeeb, thiab tau pom tias muaj txiaj ntsig zoo rau lwm cov SERDs ua ntej siv kho mob. Qhov ncauj giredestrant muaj peev xwm hloov tau cov kev kho mob ntawm cov neeg mob. Piv nrog rau kev txhaj tshuaj intramuscular, nws muab kev kho mob nrog kev yooj yim dua thiab mob tsawg dua.

Cov ntaub ntawv tshawb xyuas ib ntus los ntawm 83/202 cov neeg mob rau npe hauv coopERA txoj kev tshawb fawb mob qog noj ntshav qhia tau tias piv nrog anastrozole, giredestrant muaj kev tiv thaiv zoo dua thiab muaj kev nyab xeeb zoo hauv HR-zoo thiab HER2-negative mob cancer mis:

Thaum lub sij hawm lub qhov rais ntawm lub sij hawm (1-14 hnub) rau no neoadjuvant (preoperative) txoj kev tshawb no, tus txheeb ze Ki67 txo tau siv raws li ib tug proliferation biomarker los soj ntsuam cov pharmacodynamic nyhuv ntawm giredestrant, uas qhia tau hais tias lub peev xwm ntawm kev kho mob los inhibit qog loj hlob: ( 1) Ki67 ntawm giredestrant raug txo los ntawm qhov nruab nrab ntawm 80% (95% CI: -85%, -72%), thaum Ki67 ntawm anastrozole raug txo los ntawm qhov nruab nrab ntawm 67% (95% CI; 95% CI: -75). %, -56%), p=0.0222. (2) Hauv cov neeg mob uas muaj kab mob hauv paus Ki67 ≥ 20% lossis lub hauv paus Ki67< 20%,="" qhov="" sib="" npaug="" ki67="" inhibition="" tau="" pom="" nrog="" kev="" kho="" mob="" giredestrant="" (baseline="" ki67="" ≥="" 20%="" pejxeem:="" 83%="" vs="" 71%;="" hauv="" paus="" ki67<="" ;="" 20%="" pejxeem="" nruab="" nrab:="" 65%="" vs="" 24%).="" (3)="" tom="" qab="" 14="" hnub="" ntawm="" kev="" kho="" mob,="" 25%="" ntawm="" cov="" qog="" nqaij="" hlav="" hauv="" pawg="" kho="" mob="" giredestrant="" pom="" qhov="" ua="" tiav="" ntawm="" lub="" voj="" voog="" ntawm="" tes="" raug="" ntes="" (ccca),="" thiab="" anastrozole="" yog="" 5%="" (δ20%;="" 95%="" ci:="" -37%="" thiab="" -3%="" ).="" kev="" nyab="" xeeb="" ntawm="" giredestrant="" yog="" ua="" raws="" li="" nws="" cov="" txheej="" txheem="" ntawm="" kev="" ua,="" thiab="" cov="" kev="" mob="" tshwm="" sim="" cuam="" tshuam="" nrog="" giredestrant="" (28%)="" yog="" tsawg="" dua="" li="" ntawm="" anastrozole="" (38%).="" tsis="" muaj="" qhov="" tshwm="" sim="" tsis="" zoo="" (ae)="" lossis="" cov="" xwm="" txheej="" tsis="" zoo="" tshwm="" sim="" ≥="" qib="" 3="" cuam="" tshuam="" nrog="">