I-Enfortumab vedotin-ejfv ene-pembrolizumab igunyazwe yi-USFDA ngomdlavuza we-urothelial othuthukile endaweni noma we-metastatic

Kusukela ngomhla ka-15 Disemba 2023, i-Food and Drug Administration (FDA) igunyaze i-enfortumab vedotin-ejfv (Padcev, Astellas Pharma) kanye i-pembrolizumab (Keytruda, Merck) kubantu abane-carcinoma ethuthukisiwe endaweni noma ye-metastatic urothelial (la/mUC). I-FDA ngaphambilini inikeze ukugunyaza okusheshayo kule nhlanganisela ezigulini ezinomdlavuza we-urothelial othuthukile wasendaweni noma we-metastatic ongakwazi ukuthola ukwelashwa okuqukethe i-cisplatin.

Ucwaningo lubheke ukuthi lusebenze kahle kangakanani ku-EV-302/KN-A39 (NCT04223856), uhlolo olungahleliwe, olunelebula evulekile nabantu abangu-886 ababenomdlavuza we-urothelial othuthukisiwe endaweni futhi abangazange babe nokwelashwa okuhlelekile kokugula okuthuthukile ngaphambili. Iziguli zanikezwa ngokungahleliwe i-enfortumab vedotin-ejfv ene-pembrolizumab noma i-chemotherapy esekelwe ku-platinum (i-gemcitabine ene-cisplatin noma i-carboplatin). Ukungahleliwe kufakwe kusigaba ngokusekelwe ekufanelekeni kwe-cisplatin, isisho se-PD-L1, kanye nokuba khona kwama-metastase esibindi.

Izinyathelo eziyinhloko ezisebenzayo kwaba ukusinda sekukonke (i-OS) kanye ne-progression-free survival (PFS) ehlolwe ithimba lokubuyekeza elimaphakathi elingathathi hlangothi ngaphandle kokuchema.

I-Enfortumab vedotin-ejfv plus pembrolizumab ibonise ukuthuthuka okuphawulekayo kwezibalo kukho konke ukusinda (OS) kanye nokusinda kwe-progression-free (PFS) uma kuqhathaniswa nokwelashwa okusekelwe ku-platinum. Ukusinda sekukonke kwaba yizinyanga ezingama-31.5 (95% CI: 25.4, akunakulinganiswa) ezigulini ezelashwe nge-enfortumab vedotin-ejfv plus pembrolizumab, kanye nezinyanga eziyi-16.1 (95% CI: 13.9, 18.3) kulabo abathole i-chemotherapy-based. Isilinganiso sengozi sasingu-0.47 (95% CI: 0.38, 0.58) ngenani lika-p elingaphansi kuka-0.0001. Ukusinda kwe-median progression-free survival (PFS) kwakuyizinyanga ezingu-12.5 (95% CI: 10.4, 16.6) ezigulini ezelashwe nge-enfortumab vedotin-ejfv plus pembrolizumab, kanye nezinyanga ezingu-6.3 (95% CI: 6.2, 6.5) kulabo abathole iplatinum- i-chemotherapy esekelwe. Isilinganiso sengozi (HR) sasingu-0.45 (95% CI: 0.38, 0.54) enenani lika-p elingaphansi kuka-0.0001.

Ukusabela okungekuhle kakhulu (≥20%) okubonwa ezigulini ezilashwa nge-enfortumab vedotin-ejfv kuhlanganiswe ne-pembrolizumab kufaka phakathi ukungahambi kahle kweselabhorethri njengokukhuphuka kwe-aspartate aminotransferase, ukwanda kwe-creatinine, ukuqubuka, ukukhuphuka kweglucose, i-peripheral neuropathy, ukwanda kwe-lipase, ukwehla kwama-lymphocyte, ukwanda kwe-alanine aminotransferase, ukuncipha kwe-hemoglobin, ukukhathala, ukwehla kwe-sodium, ukwehla kwe-phosphate, ukwehla kwe-albumin, pruritus, isifo sohudo, i-alopecia, ukuncipha kwesisindo, ukuncipha kwesifiso sokudla, ukwanda kwe-urate, ukwehla kwe-neutrophils, ukwehla kwe-potassium, iso elomile, isicanucanu, ukuqunjelwa, ukwanda kwe-potassium, i-dysgeusia. , ukutheleleka komgudu womchamo, nokuncipha kwamaplatelet.

Umthamo ophakanyisiwe we-enfortumab vedotin-ejfv uhlanganiswe ne-pembrolizumab ngu-1.25 mg/kg (ufika ku-125 mg ezigulini ezinesisindo esingu-100 kg noma ngaphezulu) unikezwe njengomjovo othatha imizuzu engama-30 ngezinsuku 1 no-8 zomjikelezo wezinsuku ezingama-21 kuze kube ukuqhubeka kwesifo noma imiphumela emibi engabekezeleleki.

Umthamo ophakanyisiwe we-pembrolizumab uma uhlanganiswe ne-enfortumab vedotin-ejfv ngu-200 mg onikezwa ngokufakwa emthanjeni njalo emavikini ama-3 noma ama-400 mg njalo emavikini ayisi-6 kuze kube yilapho isifo sikhula, ubuthi obungabekezeleleki, noma iminyaka emibili yokwelashwa.