PARP Inhibitor Lynparza (olaparib) Pom Zoo: Kev Kho Mob Ntawm BRCA-hloov pauv Advanced Prostate Cancer (mCRPC)!

AstraZeneca (AstraZeneca) thiab Merck& Co. (Merck& Co) tsis ntev los no tshaj tawm tias Tuam Tshoj Kev Kho Mob Cov Khoom Siv Hauv Tebchaws (NMPA) tau pom zoo raws li Lynparza (olaparib) rau qhov taw qhia tshiab: raws li kev kho mob monotherapy rau cov neeg laus Cov neeg mob metastatic castration-resistant prostate cancer (mCRPC) uas nqa cov kab mob lossis somatic BRCA hloov pauv (gBRCAm lossis sBRCAm) thiab tsis tau ua tiav kev kho yav dhau los (suav nrog hom tshiab ntawm kev kho tshuaj hormone [abiraterone acetate, enzalutamide]). Qhov kev pom zoo no hais txog qhov tseem ceeb ntawm kev hloov pauv BRCA hauv cov neeg mob qog noj ntshav prostate. Kev hloov pauv BRCA yog pab pawg me me ntawm kev kho kom rov zoo sib xws (HRR) hloov pauv noob.

Nws tsim nyog hais tias Lynparza yog thawj PARP inhibitor pom zoo hauv Suav teb rau kev kho mob qog noj ntshav prostate thiab tsuas yog PARP inhibitor uas tuaj yeem txhim kho kev muaj sia nyob tag nrho (OS) ntawm cov neeg mob nrog BRCA hloov pauv mCRPC piv nrog kev kho tshuaj tshiab (NHT) ) Tus neeg saib xyuas. Qhov kev pom zoo no qhib lub sijhawm tshiab ntawm cov tshuaj muaj tseeb rau mob qog noj ntshav hauv Suav teb. Lynparza muab cov phiaj xwm kev kho mob rau cov neeg mob qog noj ntshav prostate qib siab ntawm qib molecular. Cov neeg mob no muaj qhov ua tsis tau zoo yav dhau los thiab qee qhov kev xaiv kho.

Lynparza yog lub ntiaj teb' thawj PARP inhibitor. Raws li tam sim no, cov tshuaj tau pom zoo kho 4 hom mob qog noj ntshav, suav nrog: mob qog noj ntshav ntawm zes qe menyuam, mob qog noj ntshav, mob qog noj ntshav, thiab mob qog noj ntshav prostate. Hauv Suav teb, Lynparza tau pom zoo rau 3 qhov qhia. Yav dhau los, Lynparza tau pom zoo los ntawm NMPA rau: (1) platinum-rhiab heev epithelial zes qe menyuam mob qog noj ntshav, mob qog noj ntshav, lossis ua rau mob qog noj ntshav thawj zaug hauv cov neeg laus nrog platinum-muaj tshuaj kho mob kom ua tiav lossis ib nrab tshem tawm kev kho kho; (2)) Kev saib xyuas kev kho mob ntawm cov neeg laus uas tau kho tshiab nrog cov kab mob lossis somatic BRCA hloov pauv (gBRCAm lossis sBRCAm) ntawm kev mob qog noj ntshav epithelial qib siab, mob qog noj ntshav hauv lub cev lossis mob qog noj ntshav thawj zaug tom qab thawj kab platinum-muaj tshuaj kho mob tau ua tiav lossis ib nrab kev zam txim.

Hauv Suav teb, mob qog noj ntshav yog mob qog noj ntshav feem ntau thib rau hauv txiv neej. Muaj txog 115,000 tus neeg mob kuaj mob tshiab txhua xyoo, thiab kwv yees li 7% ntawm cov neeg mob muaj cov kab mob hloov pauv BRCA. Cov neeg mob qog noj ntshav prostate nrog cov kev hloov pauv no muaj kev kwv yees ntau dua li cov tsis muaj kev hloov pauv zuj zus. Hauv Suav teb, kwv yees li 70% ntawm cov neeg mob qog noj ntshav prostate tau mob hnyav dua thaum lub sijhawm kuaj mob, thiab lub sijhawm nyob nruab nrab ntawm cov neeg mob mCRPC tsawg dua 2 xyoos.

Kev pom zoo NMPA yog ua raws cov pab pawg cais cov txiaj ntsig ntawm Phase III PROfound trial. Txoj kev tshawb no yog thawj theem III kev tshawb fawb los tshuaj xyuas lub hom phiaj tshuaj hauv biomarker-xaiv cov neeg mob qog noj ntshav prostate nrog cov txiaj ntsig zoo. Cov pab pawg tshawb fawb tsom pom tias piv nrog cov tshuaj saib xyuas tus qauv Xtandi (enzalutamide) los yog Zytiga (abiraterone acetate hmoov), Lynparza tau txhim kho kev kho kab mob qog noj ntshav tsis muaj kev vam meej (rPFS) thiab muaj sia nyob tag nrho hauv cov txiv neej cov neeg mob nrog BRCA1/2 kev hloov pauv hauv mCRPC (OS).

Cov ntaub ntawv tshwj xeeb yog: hauv cov neeg mob BRCA1/2 hloov pauv hauv mCRPC, piv nrog Xtandi lossis Zytiga, Lynparza: (1) txo qhov kev pheej hmoo ntawm kev kis mob lossis tuag los ntawm 78% (HR=0.22, p< 0.0001)="" ,="" thiab="" ua="" rau="" rpfs="" ntev="" heev="" (nruab="" nrab:="" 9.8="" lub="" hlis="" vs="" 3.0="" lub="" hlis);="" (2)="" txoj="" kev="" pheej="" hmoo="" ntawm="" kev="" tuag="" raug="" txo="" los="" ntawm="" 37%="" (hr="0.63)," thiab="" os="" tau="" txuas="" ntxiv="" mus="" ntev="" (nruab="" nrab:="" 20.1="" hli="" vs="" 14.4="">

Lynparza (olaparib) yog thawj-ntawm-nws-zoo qhov ncauj poly-ADP ribose polymerase (PARP) inhibitor uas tuaj yeem ua kom zoo dua ntawm qhov tsis xws luag ntawm cov qog DNA kho kev puas tsuaj (DDR) txoj hauv kev rau tshwj xeeb tshaj yog tua cov qog nqaij hlav cancer. Hom kev ua no muab kev kho Lynparza uas muaj DNA puas kho qhov tsis xws Lub peev xwm ntawm ntau hom qog nqaij hlav.

Lynparza yog lub ntiaj teb' thawj PARP inhibitor, thiab nws tau pom zoo thawj zaug los ntawm Asmeskas FDA thaum Lub Kaum Ob Hlis 2014. AstraZeneca thiab Merck tau mus txog thoob ntiaj teb txoj haujlwm koom tes hauv oncology thaum Lub Xya Hli 2017 los sib koom tsim thiab lag luam Lynparza thiab lwm MEK inhibitor, selumetinib, los kho ntau hom qog nqaij hlav.

Hauv qeb PARP inhibitors, Lynparza muaj qhov nthuav dav tshaj plaws thiab ua tiav kev sim tshuaj kho mob. AstraZeneca thiab Merck tau sib koom tes los tshuaj xyuas lub peev xwm ntawm Lynparza ua kev kho mob ib leeg thiab kho ua ke rau ntau hom qog nqaij hlav.

Tam sim no, ob tog tseem tab tom ua lwm qhov kev sim ntawm Lynparza hauv kev kho mob qog noj ntshav prostate, suav nrog ntu III PROpel mus sib hais, uas tshuaj xyuas Lynparza ua thawj txoj kev kho mob ua ke nrog abiraterone thiab abiraterone ib leeg hauv kev kho mob mCRPC cov neeg mob nrog lossis tsis muaj kev hloov pauv ntawm HRR. Cov ntaub ntawv tshawb fawb xav tias yuav muaj nyob hauv ib nrab ntawm xyoo 2021.