Agasti 2023: I-Dostarlimab-gxly (i-Jemperli, i-GlaxoSmithKline), ilandelwa yi-dostarlimab-gxly njenge-ejenti eyodwa, yagunyazwa yi-Food and Drug Administration yokwelapha umdlavuza we-endometrial osezingeni eliphezulu noma ophindelelayo (EC) ongenakho ukuhambisana kahle (dMMR), njengoba kunqunywa ukuhlolwa okugunyazwe yi-FDA, noma ukungasebenzi kahle kwe-microsatellite-high (MSI-H).
I-RUBY (NCT03981796), isilingo esilawulwa ngokungahleliwe, esimaphakathi, esingaboni kabili, esilawulwa yi-placebo, ukusebenza okuhloliwe. Iqembu elincane elinqunywe kusengaphambili leziguli eziyi-122 ezine-dMMR/MSI-H EC eyinhloko ethuthukisiwe noma ephindaphindayo lenze ukuhlolwa kokusebenza kahle. Lapho idatha yendawo ingatholakali, ukuhlola okumaphakathi (IHC) kusetshenziswa Iphaneli ye-Ventana MMR RxDx yasetshenziswa ukuze kuhlolwe isimo sesimila se-MMR/MSI.
Iziguli zabelwa ngokungahleliwe (1:1) ukuze zithole noma iyiphi i-placebo ene-carboplatin ne-paclitaxel, ilandelwe yi-placebo, noma i-dostarlimab-gxly ene-carboplatin ne-paclitaxel, ilandelwe yi-dostarlimab-gxly. Isixhumanisi esishiwo ngenhla sinikeza imininingwane enemininingwane yemithi eminingi ye-chemotherapy. Isimo se-MMR/MSI, iradiation yangaphandle ye-pelvic yangaphambili, kanye nesigaba sesifo (okuphindaphindiwe, iSigaba III esiyinhloko, noma iSigaba IV esiyinhloko) konke kwacatshangelwa lapho kuhlelwa inqubo ye-randomization.
Ukusinda okungenayo i-progression-free survival (PFS) okuhlolwe umphenyi kusetshenziswa i-RECIST v. 1.1 kwakuyisilinganiso somphumela esiyinhloko sokusebenza ngempumelelo. Nge-PFS emaphakathi yezinyanga ezingu-30.3 uma iqhathaniswa nezinyanga ezingu-7.7 (I-Hazard Ratio=0.29 [95% CI: 0.17, 0.50]; p-value0.0001) yemithi equkethe i-dostarlimab-gxly ne-placebo, ngokulandelana, kubonakale ukuthuthukiswa kwe-PFS okubalulekile ngokwezibalo. eqenjini le-dMMR/MSI-H.
I-Pneumonitis, i-colitis, i-hepatitis, i-endocrinopathies efana ne-hypothyroidism, i-nephritis enokuhluleka kwezinso, kanye nokusabela okubi kwesikhumba kuyizibonelo zokusabela okubi okubangelwa amasosha omzimba okungenzeka nge-dostarlimab-gxly. Ukuqubuka, isifo sohudo, i-hypothyroidism, nomfutho wegazi ophakeme kwakuyizehlakalo ezimbi kakhulu (20%) ezine-dostarlimab-gxly kuhlanganiswe ne-carboplatin ne-paclitaxel. Ukuze uthole uhlu oluphelele lwemiphumela emibi, bheka ulwazi olunqunyiwe.
I-Dostarlimab-gxly kufanele inikezwe ngethamo elingu-500 mg njalo emavikini amathathu ngemithamo eyisithupha ye-carboplatin ne-paclitaxel, bese kuba ngu-1,000 mg kanye emavikini ayisithupha kuze kuqhubeke ukugula noma kuba nobuthi obungabekezeleleki, obungathatha iminyaka emithathu. Uma inikezwa ngosuku olufanayo nokwelapha ngamakhemikhali, i-dostarlimab-gxly kufanele inikezwe kuqala.
Buka imininingwane egcwele ye-Jemperli.
