Verzenio (abemaciclib) cov ntaub ntawv tshiab: thawj CDK4 / 6 inhibitor los kho mob cancer mis thaum ntxov!--2/2

Thaum Lub Kaum Hli 2021, US FDA tau pom zoo Verzenio ua ke nrog kev kho mob endocrine (tamoxifen lossis aromatase inhibitor) raws li kev kho mob ntxiv rau HR+/HER2-muaj kev pheej hmoo siab mob qog noj ntshav thaum ntxov (EBC) cov neeg laus. Tshwj xeeb: HR+/HER2- EBC cov neeg mob uas muaj cov qog ntshav qab zib zoo, muaj kev pheej hmoo siab rov qab los, thiab FDA-pom zoo cov kev sim txiav txim siab yog Ki-67 cov qhab nia ≥20%. Ki-67 yog lub cim ntawm kev loj hlob ntawm tes.

Nws tsim nyog hais tias Verzenio yog thawj zaug thiab tsuas yog CKD4/6 inhibitor pom zoo rau cov neeg mob saum toj no. Tsis tas li ntawd, hauv kev kho mob ntawm HR+/HER2- EBC, Verzenio yog thawj cov tshuaj ntxiv rau kev kho mob endocrine tau pom zoo los ntawm FDA hauv ob xyoo dhau los. Cov ntaub ntawv los ntawm theem 3 monarchE txoj kev tshawb fawb pom tau tias nyob rau hauv cov neeg mob nrog HR+/HER2- EBC nrog cov qog nqaij hlav zoo thiab muaj kev pheej hmoo siab rov qab los, Verzenio ua ke nrog ET kev kho mob pom tau tias muaj kev pheej hmoo tseem ceeb ntawm cov kab mob rov ua dua piv nrog tus qauv adjuvant. endocrine therapy (ET) Thiab txo qhov tseem ceeb ntawm kev kho mob.

Kev pom zoo los ntawm FDA yog raws li cov pov thawj uas twb muaj lawm los ntawm Verzenio, uas yav dhau los tau pom zoo rau kev kho mob ntawm qee hom HR+/HER2- qib siab lossis mob qog nqaij hlav cancer mis. Tib lub sijhawm raws li qhov kev pom zoo no, FDA kuj tau nthuav dav kev siv Verzenio hauv txhua qhov kev qhia, suav nrog cov txiv neej cov neeg mob thaum ua ke nrog kev kho endocrine (ET). Verzenio ntsiav tshuaj specifications yog 200mg, 150mg, 100mg, 50mg.

Qhov kev pom zoo no yog los ntawm cov txiaj ntsig ntawm kev tshuaj xyuas kev ua tau zoo ntawm pawg thawj coj saib xyuas huab tais thiab kev soj ntsuam ntxiv tom qab qhov tshwm sim. Hauv qhov kev tshuaj ntsuam no, Verzenio ua ke nrog ET txuas ntxiv qhia cov txiaj ntsig tseem ceeb hauv kev kho mob: Rau cov neeg mob uas muaj kev pheej hmoo siab kho mob thiab cov kab mob pathological thiab Ki-67 tau qhab nia ≥20%, Verzenio+ET piv nrog tus qauv adjuvant ET yuav ua rau lub mis. mob qog noj ntshav rov qab los yog qhov kev pheej hmoo ntawm kev tuag raug txo los ntawm 37% (HR=0.626; 95% CI: 0.49-0.80), thiab qhov txiaj ntsig zoo ntawm IDFS qhov xwm txheej hauv 3 xyoos yog 7.1%. Hauv qhov kev tshuaj ntsuam no, tus naj npawb ntawm IDFS qhov xwm txheej hauv Verzenio+T pab pawg ET yog 104, thaum nyob hauv pawg ET yog 158. Cov ntaub ntawv muaj sia nyob tag nrho (OS) tseem tsis tau paub tab, thiab kev soj ntsuam txuas ntxiv txuas ntxiv mus. . Hauv qhov kev sim no, qhov tsis zoo tshwm sim tau ua raws li kev paub txog kev nyab xeeb ntawm Verzenio.

Mob qog noj ntshav mis yog mob qog noj ntshav ntau tshaj plaws ntawm cov poj niam thoob ntiaj teb. Nws kwv yees tias 90% ntawm cov qog nqaij hlav hauv lub mis raug kuaj pom thaum ntxov. Kwv yees li 70% ntawm cov qog nqaij hlav mis yog HR+/HER2-, uas yog hom kab mob ntau tshaj plaws. Txawm nyob rau hauv HR+/HER2- subtype, mob qog noj ntshav mis yog ib yam kab mob nyuaj, thiab ntau yam-xws li seb tus mob qog noj ntshav tau kis mus rau cov qog nqaij hlav, cov yam ntxwv ntawm cov qog-yuav ua rau muaj kev pheej hmoo ntawm kev rov tshwm sim dua. .

Lub active tshuaj muaj nyob rau hauv Verzenioabemacclib, uas yog lub hom phiaj ntawm qhov ncauj CDK4/6 inhibitor uas muaj peev xwm xaiv tau inhibit cyclin-dependent kinase 4/6 (CDK4/6), rov qab tswj lub voj voog ntawm tes, thiab thaiv cov qog hlwb proliferation. Lub voj voog ntawm tes tsis tswj hwm yog ib qho tseem ceeb ntawm kev mob qog noj ntshav. CDK4/6 yog overactive nyob rau hauv ntau yam mob qog noj ntshav, ua rau lub cell proliferation uncontrolled. CDK4/6 yog tus tswj hwm lub voj voog ntawm tes, uas tuaj yeem ua rau kev hloov pauv ntawm lub voj voog ntawm tes los ntawm theem kev loj hlob (G1 theem) mus rau DNA replication theem (S1 theem). Hauv cov tshuaj estrogen receptor zoo (ER{13}}) mob qog noj ntshav mis, kev ua haujlwm dhau ntawm CDK4/6 yog nquag heev, thiab CDK4/6 yog lub hom phiaj tseem ceeb ntawm ER signaling. Cov ntaub ntawv hauv tsev kho mob qhia tau tias ob qhov inhibition ntawm CDK4/6 thiab ER signaling muaj kev sib koom ua ke thiab tuaj yeem cuam tshuam kev loj hlob ntawm ER+ cov qog nqaij hlav cancer mis hauv G1 theem. Cov pov thawj kho mob kuj qhia tau tiasabemacclibhla cov ntshav-hlwb barrier. Hauv cov neeg mob qog noj ntshav siab, suav nrog cov neeg mob qog noj ntshav mis, qhov concentration ntawm abemaciclib thiab nws cov metabolites nquag (M2 thiab M20) hauv cov kua cerebrospinal yog sib npaug rau qhov tsis muaj ntshav plasma concentration.

Verzenio tau txais kev pom zoo rau kev lag luam thaum Lub Kaum Hli 2017 rau kev kho mob ntawm cov neeg mob HR+/HER2- qib siab lossis mob qog nqaij hlav cancer mis. Cov tshuaj tsim nyog rau: (1) Ua ke nrog aromatase inhibitor (AI) raws li kev kho mob endocrine thawj zaug rau kev kho cov poj niam postmenopausal (2) Ua ke nrog fulvestrant rau cov poj niam uas tau nce hauv kev kho endocrine; (3) Raws li kev kho mob monotherapy, nws yog siv rau cov neeg laus cov neeg mob uas tau txais kev kho mob endocrine thiab kws khomob los tswj cov kab mob metastatic tab sis tau ua tiav.

Tam sim no, muaj ntau CDK4/6 inhibitors ntawm lub khw, ntxiv rau Eli Lilly's Verzenio, Pfizer's Ibrance (palbociclib) thiab Novartis's Kisqali (ribociclib). Hauv Suav teb, Pfizer Ibrance (palbociclib) tau pom zoo thaum Lub Yim Hli 2018 thiab tau los ua thawj CDK4/6 inhibitor pom zoo hauv Suav teb. Cov tshuaj qhia yog: ua ke nrog aromatase inhibitors raws li kev kho mob endocrine thawj zaug rau HR+/HER2- Kev kho mob ntawm cov poj niam tom qab yug me nyuam nrog mob qog noj ntshav hauv zos lossis mob qog noj ntshav.

Thaum Lub Kaum Ob Hlis 2020, Eli Lilly Verzenio (abemacclib) tau pom zoo thiab dhau los ua tus thib ob CDK4/6 inhibitor pom zoo hauv Suav teb. Cov tshuaj no yog siv los kho HR+/HER2- mob qog noj ntshav hauv zos lossis mob qog noj ntshav metastatic: (1) thiab aroma Kev siv cov enzyme inhibitors ua thawj zaug kev kho mob endocrine rau cov poj niam postmenopausal; (2) Kev siv ua ke nrog fulvestrant rau cov neeg mob uas tau ntsib cov kab mob tshwm sim tom qab tau txais kev kho mob endocrine.

Thaum Lub Peb Hlis 8, 2021, Eli Lilly tau tuav lub rooj sib tham xov xwm hauv Beijing thiab Shanghai tib lub sijhawm: CDK4/6 inhibitor Verzenio (abemacclib) tau ua tiav hauv Suav teb.