I-FDA ibuyekeza inkomba ye-pembrolizumab yomdlavuza wesisu

I-Food and Drug Administration ibuyekeze ukusetshenziswa okugunyaziwe kwe-pembrolizumab (Keytruda, Merck) ngokuhlanganiswa ne-trastuzumab, i-fluoropyrimidine, kanye ne-chemotherapy equkethe i-platinum yokwelapha i-HER2-positive gastric noma i-gastroesophageal junction adenocarcinoma ethuthuke kakhulu endaweni, engalungiseki, noma abakaze bathole ukwelashwa kwangaphambili. Ukugunyazwa okubuyekeziwe kukhawulela ukusetshenziswa kwalesi sibonakaliso ezigulini ezinamathumba aveza i-PD-L1 (CPS ≥ 1) njengoba kutholwe ukuhlolwa okugunyazwe yi-FDA, kuyilapho zisahambisana nemithetho yokugunyazwa esheshisiwe.

I-FDA igunyaze i-Agilent PD-L1 IHC 22C3 pharmDx njengethuluzi lokuxilonga elihambisanayo lokuhlonza iziguli ezine-gastric noma i-GEJ adenocarcinoma izimila zazo ezine-PD-L1 expression (CPS ≥ 1).

The effectiveness was assessed in KEYNOTE-811 (NCT03615326), a study conducted at many centers, where patients with HER2-positive locally advanced or metastatic gastric or GEJ i-adenocarcinoma who had not undergone systemic therapy for metastatic illness were randomly assigned to receive either the treatment or a placebo in a double-blind manner. Patients were randomly assigned to receive either pembrolizumab 200 mg intravenously or a placebo every 2 weeks along with trastuzumab and either fluorouracil plus cisplatin or capecitabine plus oxaliplatin in a 1:1 ratio.

Iziphetho eziyinhloko ezisebenzayo ze-KEYNOTE-811 ukusinda sekukonke (OS) kanye nokusinda kwe-progression-free (PFS). Ukugunyazwa ngoMeyi 5, 2021, kwanikezwa ngemva kokuhlola ukuhlaziywa kwesikhashana kwesilinganiso sokuphendula okuhlosiwe (ORR) kanye nobude besikhathi sokuphendula (DOR). I-ORR ne-DOR zahlolwa kubahlanganyeli bokuqala abangama-264 abangahleliwe ngaleso sikhathi. Izinga lokuphendula elihlosiwe (ORR) lalingu-74% (95% CI: 66, 82) eqenjini le-pembrolizumab plus chemotherapy kanye nama-52% (95% CI: 43, 61) kuqembu le-placebo kanye ne-chemotherapy (i-p-value <0.0001) . Isikhathi esimaphakathi sokuphendula sasiyizinyanga ezingu-10.6 (ububanzi: 1.1 kuya ku-16.5) nezinyanga ezingu-9.5 (ububanzi: 1.4 kuya ku-15.4) emaqenjini ahlukene.

Ukuhlaziywa kwesikhashana kohlolo olubhaliswe ngokugcwele nabahlanganyeli abangu-698 kubonise ukuthi kusethi engaphansi yeziguli eziyi-104 ezine-PD-L1 CPS <1, ama-hazard ratios (HR) okusinda okuphelele (OS) kanye nokusinda ngaphandle kokuqhubekela phambili (PFS) bekuyi-1.41 ( 95% CI 0.90, 2.20) kanye 1.03 (95% CI 0.65, 1.64) ngokulandelana.

Iphrofayili yokuphepha yeziguli ezilashwa nge-pembrolizumab ne-trastuzumab + chemotherapy ku-KEYNOTE-811 yayifana namaphrofayili okuphepha amisiwe e-trastuzumab + chemotherapy yedwa noma i-pembrolizumab monotherapy.

Umthamo ophakanyisiwe we-pembrolizumab ngu-200 mg njalo emavikini angu-3 noma u-400 mg njalo emavikini angu-6 kuze kube yilapho isifo siqhubeka, ubuthi obungabekezeleleki, noma isikhathi esiphezulu sezinyanga ezingu-24. Sebenzisa i-pembrolizumab ngaphambi kwe-trastuzumab kanye ne-chemotherapy uma kunikezwa ngosuku olufanayo.