I-Pembrolizumab ene-chemoradiotherapy igunyazwe yi-USFDA ye-FIGO 2014 Stage III-IVA umdlavuza womlomo wesibeletho

I-Food and Drug Administration igunyaze i-pembrolizumab (Keytruda, Merck) ihlanganiswe ne-chemoradiotherapy (CRT) yeziguli ezinomdlavuza womlomo wesibeletho we-FIGO 2014 Isigaba III-IVA ngoJanuwari 12, 2024.

Ucwaningo olubizwa nge-KEYNOTE-A18 (NCT04221945) lubheke ukuthi lusebenze kahle kangakanani. Kwakuyisivivinyo esilawulwa yi-multicenter, esingahleliwe, esingaboni kabili, esilawulwa yi-placebo esineziguli zomdlavuza womlomo wesibeletho eziyi-1060 ezazingakaze zihlinzwe ngaphambili, ngemisebe, noma ukwelashwa kwe-systemic. Kwakukhona abantu abangu-596 ovivinyweni abane-FIGO 2014 Stage III-IVA isifo kanye nabantu abangu-462 abane-FIGO 2014 Stage IB-IIB isifo ababenesifo se-node-positive.

Abahlanganyeli babelwa ngokungahleliwe ukuthi bathole i-pembrolizumab 200 mg noma i-placebo njalo emavikini angu-3 emijikelezweni emi-5 kanye ne-CRT. Njalo emavikini ayisithupha emijikelezweni engu-15, i-pembrolizumab 400 mg noma i-placebo iza ngemva kwalokhu. Umuthi we-CRT wawuhlanganisa i-cisplatin ngethamo lika-40 mg/m2 elinikezwe ngomthambo kanye ngesonto emijikelezweni emi-5, okungenzeka kube nomjikelezo owengeziwe wesi-6, kanye nokwelashwa ngemisebe yangaphandle (EBRT) kanye i-brachytherapy. I-Randomization yahlelwa ngokusekelwe ohlotsheni oluhlosiwe lokwelashwa ngemisebe yangaphandle (EBRT), isigaba somdlavuza, kanye nomthamo ophelele wokushiswa kwemisebe.

Izinkomba zokusebenza eziyinhloko zazihlanganisa ukusinda kwe-progression-free (PFS) okuhlolwe umphenyi ngokusekelwe kumbandela we-RECIST v1.1 noma ukuqinisekiswa kwe-histopathologic, kanye nokusinda sekukonke (OS). Uhlolo lubonise ukuthuthuka okuphawulekayo kwezibalo ku-progression-free survival (PFS) kulo lonke iqembu. Ukuhlaziywa kweqembu elincane lokuhlola kwenziwa ezigulini ezingama-596 ezine-FIGO 2014 Stage III-IVA yokugula. Isilinganiso sesilinganiso sengozi ye-PFS sasingu-0.59 (95% CI: 0.43, 0.82). Engalweni ye-pembrolizumab, ama-21% eziguli athole umcimbi we-PFS uma kuqhathaniswa nama-31% engalweni ye-placebo. Ukuhlaziywa kweqembu elincane lokuhlola kwenziwa ezigulini ze-462 ezine-FIGO 2014 Stage IB2-IIB isifo. Isilinganiso se-PFS HR sasingu-0.91 (95% CI: 0.63, 1.31), siphakamisa ukuthi ukuthuthukiswa kwe-PFS kubo bonke abantu kubonakale ikakhulukazi ezigulini ezine-FIGO 2014 Stage III-IVA isifo. Idatha ye-OS ayithuthukiswanga ngokwanele ngenkathi kwenziwa ukuhlaziywa kwe-PFS.

Iziguli ezinikezwe i-pembrolizumab kanye ne-chemoradiotherapy ngokuvamile ziba nemiphumela emibi efana nokucanuzela kwenhliziyo, isifo sohudo, ukuhlanza, izifo zomgudu womchamo, ukukhathala, i-hypothyroidism, ukuqunjelwa, ukungakuthandi ukudla, ukukhuluphala, ubuhlungu besisu, i-pyrexia, i-hyperthyroidism, i-dysuria, ukuqubuka, kanye ne-pelvic. ubuhlungu.

Isheduli ephakanyisiwe yomthamo we-pembrolizumab ngu-200 mg ifakwa emithanjeni njalo emavikini ama-3 noma ama-400 mg emithanjeni njalo emavikini ayi-6, iqhubeke kuze kube ukukhula kwesifo, imiphumela engemihle engabekezeleleki, noma isikhathi esifinyelela ezinyangeni ezingama-24. Sebenzisa i-pembrolizumab ngaphambi kwe-chemoradiotherapy uma inikezwe ngosuku olufanayo.