AstraZeneca Kinase Inhibitor Koselugo (selumetinib) Muaj Qhov Txiaj Ntsig Zoo Thiab Tseem Ua Rau Txo Cov Ntsej Muag Ntim

Recently, the open label II of AstraZeneca targeted anticancer drug Koselugo (selumetinib) for the treatment of symptomatic, unresectable plexiform neurofibroma (PN) in pediatric patients with neurofibromatosis type 1 (NF1) The results of the SPRINT Stratum 1 trial (NCT01362803) were published online in the New England Journal of Medicine (NEJM). The article title is: Selumetinib in Children with Inoperable Plexiform Neurofibromas.

NF1 yog kev mob caj ces ntawm cov leeg hlwb uas ua rau cov qog hlav tuaj rau ntawm txoj hlab ntshav. Cov qog no (plexiform neurofibroma) tuaj yeem loj hlob nyob txhua qhov chaw ntawm lub cev, suav nrog lub ntsej muag, nqaj, ncig lub nqaj qaum, thiab thaj chaw hauv lub cev uas tuaj yeem cuam tshuam cov kabmob. Feem ntau cov neurofibromatosis - ntsig txog cov tsos mob muaj xws li kev tsis ua hauj lwm, ua rau lub cev puas, thiab mob. Cov ntaub ntawv los ntawm SPRINT Stratum 1 kev sim siab qhia tau hais tias kev kho mob Koselugo muaj cov txiaj ntsig tseem ceeb hauv cov neeg mob, uas tuaj yeem txuas ntxiv txo cov qog ntim, txo qhov mob, txhim kho txoj haujlwm txhua hnub thiab kev noj qab haus huv tag nrho - ntsig txog lub neej zoo.

Koselugo yog qhov ncauj tawm tshiab kinase inhibitor uas tau pom zoo los ntawm Asmeskas FDA hauv nruab nrab - Lub Plaub Hlis xyoo no. Nws siv rau cov menyuam yaus mob hlwb neurofibromatosis hom 1 (NF1) hnub nyoog 2 xyoos lossis tshaj saud los kho NF1 - ntsig txog tsos mob thiab tsis tuaj yeem plex Neurofibromatosis (PN). Nws tsim nyog teev tias Koselugo yog thawj cov tshuaj pom zoo los ntawm Asmeskas FDA los kho NF1. Yav dhau los, Koselugo tau muab cov ntsuag tsim nyog rau niam txiv kev ua yeeb tshuaj (ODD) thiab kev ua txhaum kev quav tshuaj (BTD) rau kev kho NF1. Koselugo yog kinase inhibitor, lub ntsiab lus nws ua los ntawm cov enzymes tseem ceeb, thiaj li tiv thaiv kev loj hlob ntawm cov qog hlwb.

Plexus neurofibroma (PN) (Duab cov duab: cancerworld.info)

NF1 yog ib yam kab mob tsawg kawg uas muaj kev cuam tshuam, kev vam meej, thiab feem ntau ua rau lub cev tsis meej pem. Tus kab mob no feem ntau pib thaum ntxov lub neej thiab tshwm sim los ntawm kev hloov pauv lossis kev puas tsuaj hauv cov caj ces tshwj xeeb. NF1 feem ntau kuaj pom thaum ntxov rau menyuam yaus. NF1 tshwm sim hauv kwv yees li ntawm ib ntawm 3, 000 menyuam yaus thiab yog yam ntxwv hloov ntawm daim tawv nqaij (nqaij tawv), cov hlab ntsha thiab pob txha puas, thiab qhov kev pheej hmoo ntawm kev tsim cov qog nqaij hlav thiab lub cev tsis zoo hauv lub neej. 30% rau 50% ntawm cov neeg mob NF1 muaj ib lossis ntau plexiform neurofibromas (PN). Kev kho mob tseem ceeb rau PN yog kev rov phais mob. Hmoov tsis zoo, vim los ntawm qhov chaw lossis ntim ntawm cov qog, ntau tus neeg mob tsis haum rau kev phais. Ntxiv rau, NP feem ntau rov qab kuaj dua tom qab kev phais mob siab dua thiab yog li ntawd sawv cev rau thaj chaw tseem ceeb uas tsis muaj kev kho mob.

SPRINT Stratum 1 kev sim siab tau txais kev txhawb nqa los ntawm National Cancer Institute (NCI) Kev Kho Mob Ntsuam Xyuas Kev Kho Mob (CTEP). Qhov kev sim muaj npe tau 50 leej neeg mob (cov hnub nyoog muaj hnub nyoog 10,2 xyoo, thaj tsam: 3. 5-17 .4). Cov menyuam no tau NF1 Thiab tsis tuaj yeem PN (txhais tau tias PN uas tsis tuaj yeem tshem tawm tag tab sis tsis ua rau muaj kev pheej hmoo loj rau tus neeg mob). Feem ntau cov neurofibromatosis - ntsig txog cov tsos mob yog kev xiam oob khab (44 qhov xwm txheej), lub cev muaj zog (33 tus mob), thiab mob (26 mob). Hauv kev sim, cov neeg mob tau siv Koselugo 25 mg / m2 (pom zoo pom zoo) ob zaug txhua hnub kom txog thaum tus mob tsis zoo lossis tsis tsim nyog cov kev tsis haum siab tshwm sim. Hauv lub sijhawm sim, tus neeg mob & # 39; s hloov lub pob thiab hloov qog - cov tsos mob ntsig txog tus kab mob tau raug soj ntsuam ib txwm, thiab tag nrho tus lej teb (ORR) tau txiav txim siab, uas tau txhais tias: 3 {{8} } 6 lub hlis los ntawm MRI lees paub qhov ua tiav lossis ib nrab ntawm kev so (PN qog ntim txo reduction 20%).

Data published on NEJM shows that as of March 29, 2019, 35 of 50 patients had confirmed remission, that is, the total remission rate (ORR) of Koselugo twice daily oral monotherapy was 70% (n=35 / 50), all patients have partial remission (PR). Of the 35 patients with confirmed remission, 28 (80%) showed sustained remission (remission duration ≥ 1 year). In addition,

Lub sim tseem tau soj ntsuam qhov cuam tshuam ntawm Koselugo rau lwm qhov txiaj ntsig kev soj ntsuam, suav nrog kev hloov pauv hauv PN - cuam tshuam txog qhov tsis xws luag, cov tsos mob, thiab kev tsis taus zoo. Txawm hais tias tus qauv ntsuas me me ntawm cov neeg mob ntsuas txhua PN - ntsig txog qhov mob (xws li tsis xws li, qhov mob, qhov muaj zog thiab teeb meem rau qhov txav tsis taus, cua nrawm, qhov muag tsis pom kev, thiab lub zais zis los yog lub plab tsis ua haujlwm), PN - yam tsis muaj feem cuam tshuam , cov tsos mob, thiab ua haujlwm lub sijhawm kho Cov kev puas tsuaj kuj qhia txhim kho.

Tshwj xeeb: Tom qab 1 xyoos ntawm kev kho mob, tus neeg mob tau tshaj tawm cov mob qog mob tau tsawg los ntawm qhov nruab nrab ntawm 2 cov ntsiab lus, uas pom tau tias muaj kev txhim kho hauv thaj chaw kho mob. Ntxiv rau, cov haujlwm txhua hnub (38% thiab 50%, feem) thiab kev noj qab haus huv tag nrho - ntsig txog lub neej zoo (48% thiab 58%, feem) thiab lub zog (56%) thiab thaj tsam ntawm kev txav (38%) hauv cov lus ceeb toom menyuam yaus thiab niam txiv cov ntawv ceeb toom Hauv kev tshwm sim, kev txhim kho hauv tseem ceeb hauv chav kho mob tau tseem pom.

Nyob rau ntawm 3- xyoo ua raws li - nce, qhov kev vam meej - kev muaj sia nyob dawb ntawm tus kab mob hauv pawg kho mob Koselugo yog 84%, piv nrog 15% hauv cov pab pawg keeb kwm tswj hwm. Thaum lub sijhawm sim, 5 tus neeg mob txuas mus kho kev kho mob vim kev ua rau muaj kev phiv los ntawm Koselugo, thiab 6 cov neeg mob tsis zoo. Kev nquag muaj tshuaj lom neeg feem ntau yog xeev siab, ntuav, raws plab, nce asymptomatic hauv creatine phosphokinase qib, pob txuv - zoo li pob khaus, paronychia.

Koselugo & #39;s active pharmaceutical ingredient is selumetinib, which is an oral, potent and selective MEK1 / 2 kinase inhibitor. The NF1 gene encodes neurofibromin (neurofibromin), which negatively regulates the RAS / MAPK pathway and helps control cell growth, differentiation, and survival. Mutations in the NF1 gene may cause the RAS / RAF / MEK / ERK signaling pathway to become unregulated, which may cause cells to grow, divide, and replicate in an uncontrolled manner, and may cause tumor growth. Selumetinib potentially inhibits tumor growth by inhibiting the MEK enzyme in this pathway. Currently, selumetinib is being evaluated in clinical studies as a monotherapy and in combination with other therapies for the treatment of multiple tumor types.

selumetinib tau tshawb pom los ntawm Array BioPharma, thiab AstraZeneca tau tso cai rau xyoo 2003 kom tau txais cov cai tshwj xeeb thoob ntiaj teb rau lub chaw tub rog. Thaum Lub Xya Hli 2018, AstraZeneca thiab Merck tau mus txog txoj kev koom tes koom ua ke ntawm oncology los tsim kev lag luam thiab ua lag luam selumetinib thiab PARP inhibitor Lynparza thoob ntiaj teb. Tam sim no, ob tog tab tom ua lub sijhawm I / II soj ntsuam tshawb nrhiav, SPRINT, txhawm rau tshawb nrhiav cov txiaj ntsig zoo ntawm selumetinib hauv cov neeg mob uas tsis muaj kev cuam tshuam txog NF 1- ntsig txog plexiform neurofibromas (PN).

Neurofibromatosis hom 1 (NF1) yog ib hom kab mob uas tsis paub tshwm sim muaj txog li 3, 000 rau 4, 000 hauv cov menyuam mos. Tus kab mob yog tshwm sim los ntawm kev hloov pauv lossis hloov caj ces hauv caj ces ntawm NF1 caj ces thiab cuam tshuam nrog ntau cov tsos mob, suav nrog cov mos mos (subcutaneous neurofibromas) ntawm daim tawv nqaij thiab hauv daim tawv nqaij, tawv nqaij tawv nqaij (kas fes mis plaques), hauv Benign cov hlab ntsha hlav hlav (plexiform neurofibromas [PN]) kuj tseem tuaj yeem tshwm sim hauv 20% -50% ntawm cov neeg mob. Cov plexiform neurofibromas (PN) tuaj yeem ua rau mob, ua kom lub cev puas, thiab ua rau lub cev tsis ua haujlwm.

People with NF1 may experience many other complications, such as learning difficulties, twisting and bending of the spine, hypertension and epilepsy. NF1 also increases a person & #39;s risk of other cancers, including malignant brain and peripheral nerve sheath tumors and leukemia. Symptoms of the disease start early in childhood and vary greatly in severity, which can reduce life expectancy by as much as 15 years.

qhov chaw ：Selumetinib Rau Cov Menyuam Yaus Tsis Muaj Plexiform Neurofibromas