Ngokombiko wakamuva ovela e-US Centers for Disease Control and Prevention (CDC), izigameko cishe zazo zonke izinhlobo zomdlavuza ziye zehla kule minyaka engamashumi amabili edlule, kuyilapho izinga lomdlavuza wesibeletho likhuphukile. Odokotela baqala ukunaka lesi simo futhi bakhumbuza abesifazane ukuthi banake izinkinga ezimbalwa ezibalulekile zalesi sifo.
According to statistics from the American Cancer Society (ACS), more than 90% of uterine cancers occur in the endometrium, called endometrial cancer. Early endometrial cancer has a good prognosis. According to the US Centers for Disease Control and Prevention, the five-year relative survival rate is estimated to be 80% to 90%. Because umdlavuza wesibeletho can usually be diagnosed early, its most typical symptoms are abnormal bleeding before and after menopause, weight loss and pelvic pain. For advanced metastatic patients, treatment options are very limited.
Muva nje, i-US FDA igunyaze i-PD-1 inhibitor Keytruda (pabolizumab) ihlanganiswe ne-oral tyrosine kinase inhibitor Lenvima (Levatinib) ukwelapha iziguli ezinomdlavuza othile we-endometrial othuthukile. Kuyaqapheleka ukuthi lezi ziguli azidingi ukungazinzi kwe-microsatellite ephezulu (MSI-H) noma izinhlobo zokulungisa okungalungile (dMMR). Uma nje lesi sifo siqhubeka nokuthuthuka ngemva kokuthola ukwelashwa kwe-systemic kusenesikhathi futhi singakwazi ukuthola ukuhlinzwa okwelaphayo noma i-radiotherapy, le nhlanganisela yokwelapha entsha ingamukelwa.
Kumele kushiwo ukuthi lokhu kugunyazwa okusheshisiwe kwavunywa kanyekanye e-United States, Australia naseCanada.
Ukugunyazwa kusekelwe emiphumeleni yocwaningo lweziguli ezingama-94 ezinamathumba omdlavuza we-endometrial, okungekho kuzo okuyi-MSI-H noma i-dMMR. Kulezi ziguli, izinga lokuphendula eliphelele (ORR) laliyi-38.3%, kuhlanganise ne-10.6% izinga lokuphendula eliphelele (CR) kanye nezinga lokuphendula eliyingxenye lika-27.7%. I-69% (n = 25) iziguli zinesikhathi sokuphendula (DOR) ≥ izinyanga ezingu-6.
“Okungenani u-75% weziguli ezinomdlavuza we-endometrial akuzona ezohlobo lwe-MSI-H noma i-dMMR, ngakho ukuvunywa kwalokhu kwelashwa kuletha izindlela ezintsha zokwelapha nethemba ezigulini eziningi ezinomdlavuza we-endometrial.
Njengamanje, enye inqubekelaphambili yocwaningo yomdlavuza we-endometrial nayo yethulwa kafushane lapha:
I-01avelumab (i-Bavincia monoclonal antibody) ihlanganiswe ne-talazoparib (tarazopanib)
Uhlolo oluholwa u-Konstantinopoulos lusebenzise i-immune checkpoint inhibitor avelumab ngokuhlanganisa ne-PARP inhibitor talazoparib. (I-Checkpoint inhibitors ivula indlela yokuthi amasosha omzimba ahlasele umdlavuza; i-PARP inhibitors ibhubhisa amangqamuzana omdlavuza ngokuvimbela ikhono lawo lokulungisa i-DNA eyonakele.) Ocwaningweni lwangaphambilini, i-avelumab yayiyiziguli ezinomdlavuza we-endometrial “ongazinzile” ziyasebenza kakhulu, kodwa empeleni ziyasebenza kakhulu. ukungasebenzi ohlotsheni lwesifo oluvame kakhulu “isitebele se-microsatellite” (MSS). Uhlolo luzohlola ukuthi ukuhlanganisa i-avelumab ne-PARP inhibitors kusebenza kangcono ezigulini ezinesifo se-MSS.
02pembrolizumab (pabolizumab) ehlanganiswe ne-mirvetuximab
Ukuhlolwa okuhlanganisa i-checkpoint inhibitor pembrolizumab ne-mirvetuximab. (I-Pembrolizumab ihlose iphrotheni ye-immune checkpoint ebizwa ngokuthi i-PD-1; i-mirvetuximab yengeza amasosha omzimba kuma-molecule ezidakamizwa aqondise izakhiwo ezibalulekile kumaseli omdlavuza ahlukanisa ngokushesha.) Isivivinyo, esiholwa nguJennifer Veneris, MD, we-Gynecologic Oncology Project, sizohlola inhlanganisela Ukusebenza kahle iziguli ezinomdlavuza we-MSS endometrial.
03abemaciclib + LY3023414 + ukwelashwa kwehomoni
Olunye uvivinyo oluholwa u-Konstantinopoulos luzohlola inhlanganisela yesidakamizwa esihlosiwe abemaciclib + LY3023414 + i-hormone therapy. (I-LY3023414 iqondise i-enzyme yeseli lomdlavuza ebizwa ngokuthi i-PI 3 kinase; i-abemaciclib iphazamisa isigaba esibucayi somjikelezo weseli.) I-70% kuya ku-90% yomdlavuza we-endometrial ondliwa yi-estrogen futhi ekuqaleni isabela ekwelapheni okuvimba ama-hormone, kodwa ekugcineni ibuyele emuva. Ngokungeza i-abemaciclib kanye ne-LY3023414 (bangathinta izingxenye ezimbili zendlela yamangqamuzana efanayo) yokwelapha okuvimba ama-hormone, abacwaningi banethemba lokunqoba inkinga yokumelana nezidakamizwa.
04AZD1775
A trial led by Joyce Liu, MD, MPH, director of clinical research at the Department of Gynecologic Oncology at Dana-Farber, used AZD1775 for patients with high-grade serous uterine cancer that account for 10-15% of endometrial cancer. Such cancers are aggressive and usually recur after standard treatment. The recently opened trial is based on a study led by Dr. Liu and Ursula Matulonis, director of the Dana-Farber Department of Gynecologic Oncology, showing that AZD1775 is active in a patient model with high-grade serous umdlavuza wesibeletho.
I-05dostarlimab (TSR-042)
Imiphumela yohlolo lweSigaba I / II GARNET isanda kushicilelwa, futhi izinga elisebenzayo lilonke le-PD-1 inhibitor dostarlimab (TSR-042) ezigulini ezinomdlavuza we-endometrial obuyelwe kabusha noma othuthukisiwe usondele ku-30%.
Ukwengeza, kokubili ukuqina kwesathelayithi encane (MSI-H) kanye namaqembu e-micro-satellite stability (MSS) ayaqhubeka.
I-Dostarlimab (TSR-042) iyi-anti-PD-1 monoclonal antibody eyenziwe ngumuntu ngokuhlanganyela i-TESARO kanye ne-AnaptysBio. Ibophezela kumamukeli we-PD-1 ngokuhambisana okuphezulu, ngaleyo ndlela ivimbe ukubophezela kwayo ku-PD-L1 kanye ne-PD-L2 ligands.
Imiphumela yabonisa ukuthi izinga elisebenzayo laso sonke isibalo sabantu lalingu-29.6%, izinga elisebenzayo leqembu lesiguli se-MSI-H lalingu-48.8%, futhi izinga elisebenzayo kuqoqo le-MSS lalingu-20.3%. Iziguli eziyisithupha (2 MSI-H kanye 4 MSS) babe nokuxolelwa okuphelele.
Ngemva kokulandelela okumaphakathi kwezinyanga eziyi-10, ama-89% eziguli athola ukwelashwa> izinyanga eziyisi-6, kanti ama-49% eziguli athola ukwelashwa okungaphezu konyaka owodwa. Ngaphezu kwalokho, u-1% weziguli ezisebenza ngempumelelo ekwelashweni zisathola ukwelashwa.
Finally, in 85% of MSI-H responders, the total isisu burden was reduced by ≥50%, and 69% of patients with MSS had a total tumor burden of ≥50%.
I-Dostarlimab iyithemba elisha lokwelashwa komdlavuza we-endometrial.
Abacwaningi bazoqala izifundo eziqhubekayo ze-III engxenyeni yesibili ka-2019. I-Dostarlimab kanye nokwelashwa ngamakhemikhali kuzohlanganiswa nokwelashwa komugqa wokuqala womdlavuza we-endometrial, futhi sibheke phambili ekutholeni imiphumela ethembisayo maduze!
Uhlolo ngalunye lubhekana nokushiyeka kokwelashwa okujwayelekile noma izinkinga ezitholwe ekuhlolweni kwezidakamizwa okusha kwangaphambilini. Isibonelo, izivivinyo ezimbili zokuqala zihloselwe ukunqoba isimo samanje sokumpofu immunotherapy ezigulini ezinesifo se-MSS. Eyesithathu ixazulula inkinga yokumelana nokwelashwa ngama-hormone, kanti eyesine ihlose izinhlobo ezithile ezincanyana zomdlavuza we-endothelial.
Ukuze ufunde kabanzi mayelana nenqubekelaphambili yocwaningo lwakamuva kanye nohlelo olungcono kakhulu lwemithi yomdlavuza we-endometrial, ochwepheshe bomdlavuza abaphezulu kuphela ekhaya naphesheya abanolwazi olucebile lwezokwelapha. Ungafaka isicelo sokubonisana nalaba abalandelayo ochwepheshe abagunyaziwe basekhaya nabamazwe ngamazwe ukuze uthole uhlelo olungcono kakhulu lokuxilonga kanye nokwelashwa.
