I-Food and Drug Administration igunyaze i-pembrolizumab (Keytruda, Merck) ngokuhlanganiswa ne-fluoropyrimidine- kanye ne-platinum-containing chemotherapy ngomhla ka-November 16, 2023. Lokhu kugunyazwa okokwelashwa kokuqala kwabantu abadala abanezinga eliphezulu lendawo elingasahleki noma eline-metastatic HER2-negative gastric noma i-justroesophageal (GEJ) i-adenocarcinoma.
Ukusebenza kwahlolwa esivivinyweni esilawulwa yi-multicenter, esingahleliwe, esingaboni kabili, esilawulwa yi-placebo esibizwa nge-KEYNOTE-859 (NCT03675737). Uhlolo lwaluhlanganisa iziguli eziyi-1579 ezine-HER2-negative advanced gastric noma i-GEJ i-adenocarcinoma owayengakaze athole ukwelashwa okuhlelekile kwesifo se-metastatic ngaphambili. Abahlanganyeli babelwa ngokungahleliwe ukuthi bathole i-pembrolizumab 200 mg noma i-placebo kanye nokukhetha komseshi kwenhlanganisela yokwelapha ngamakhemikhali, okuhlanganisa i-cisplatin 80 mg/m2 kanye ne-5-FU 800 mg/m2/ngosuku izinsuku ezingu-5 (FP) noma i-oxaliplatin 130 mg /m2 ngoSuku 1 kanye ne-capecitabine 1000 mg/m2 kabili ngosuku izinsuku eziyi-14 (CAPOX) kumjikelezo wezinsuku ezingama-21.
Isilinganiso esiyinhloko sokusebenza kwakungukusinda okuphelele (OS). Ucwaningo luphinde lwahlola i-progression free survival (PFS), isilinganiso sokuphendula esiphelele (ORR), kanye nobude besikhathi sokuphendula (DOR) ngokusebenzisa isibuyekezo esizimele esiphuphuthekisiwe (i-BICR) ngokusekelwe kumbandela we-RECIST v1.1, enomkhawulo wezilonda ezihlosiwe eziyi-10 kanye Izilonda ezihlosiwe ezi-5 ngesitho ngasinye.
I-Pembrolizumab ehlanganiswe nokwelashwa ngamakhemikhali iholele ekuthuthukisweni okuphawulekayo kwezibalo kukho konke ukusinda (OS), ukusinda kwe-progression-free (PFS), kanye nezinga lokuphendula lenhloso (ORR). Ukusinda sekukonke kwaba yizinyanga eziyi-12.9 (95% CI: 11.9, 14.0) ne-pembrolizumab nezinyanga eziyi-11.5 (95% CI: 10.6, 12.1) ne-placebo. Isilinganiso sengozi (HR) sasingu-0.78 (95% CI: 0.70, 0.87) nevelu engu-p engu-<0.0001. Ukusinda kwe-median progression-free survival (PFS) kwakuyizinyanga ezingu-6.9 (95% CI: 6.3, 7.2) kanye nezinyanga ezingu-5.6 (95% CI: 5.5, 5.7) emaqenjini amabili, nesilinganiso sengozi (HR) esingu-0.76 [95% I-CI: 0.67, 0.85] kanye nenani lika-p elingu-<0.0001. Izinga lokuphendula lenhloso (ORR) lalingu-51% (95% CI: 48, 55) kanye no-42% (95% CI: 38, 45) ngenani elibalulekile lezibalo le-p elingaphansi kuka-0.0001 emaqenjini amabili okwelapha. Isikhathi esimaphakathi sokuphendula (DOR) kwakuyizinyanga eziyi-8 (95% CI: 7.0, 9.7) ze-pembrolizumab kanye nezinyanga ezingu-5.7 (95% CI: 5.5, 6.9) ze-placebo.
Ucwaningo olwengeziwe lwabonisa ukuthi iziguli ezanikezwa i-pembrolizumab futhi zinezimila eziveza i-PD-L1 CPS > 1 kanye ne-CPS ≥ 10 zazinokusinda okukonke kwezibalo (OS), ukusinda kokungena-progressional (PFS), kanye nezinga lokuphendula lenhloso (ORR).
I-15% yeziguli yathola ukuyeka unomphela ukwelashwa kwe-pembrolizumab ngenxa yemiphumela emibi. Imiphumela emibi eholela ekuyekeni unomphela okungenani ku-1% wezimo ihlanganisa izifo kanye nesifo sohudo.
Umthamo ophakanyisiwe we-pembrolizumab ngu-200 mg njalo emavikini angu-3 noma u-400 mg njalo emavikini angu-6 kuze kube yilapho isifo siqhubeka noma ubuthi obungabekezeleleki. Sebenzisa i-pembrolizumab ngaphambi kokwelashwa ngamakhemikhali uma inikezwa ngosuku olufanayo.
