I-Erdafitinib igunyazwe yi-USFDA nge-carcinoma ye-urothelial ethuthukisiwe endaweni noma ye-metastatic

I-Erdafitinib (i-Balversa, i-Janssen Biotech) yagunyazwa yi-Food and Drug Administration ngoJanuwari 19, 2024, ezigulini ezikhulile ezinezinguquko zofuzo ze-FGFR3 ezine-carcinoma ye-urothelial ethuthukisiwe yendawo (mUC) ethuthukisiwe noma e-metastatic. Iziguli ezibe nesifo sazo ziba zimbi kakhulu ngemva kokuthola okungenani ukwelashwa okuhleliwe okukodwa kwangaphambili ziyakufanelekela lokhu kugunyazwa, ngokusho kokuhlolwa kokuhlola okuwumngane okugunyazwe yi-FDA. I-Erdafitinib ayelulekisiwe ekwelapheni iziguli ezifanele futhi ezingakaze zithole ukwelashwa kwangaphambili kwe-PD-1 noma i-PD-L1 inhibitor. Lokhu kugunyazwa kushintsha ukusetshenziswa kwasekuqaleni kwabantu abane-metastatic urothelial carcinoma (mUC) abanokuguqulwa okuthile kuzakhi zofuzo ze-FGFR3 noma i-FGFR2 futhi asebevele belashwe nge-chemotherapy equkethe i-platinum.

I-Study BLC3001 Cohort 1 ibheke ukuthi isebenze kahle kangakanani. Kwakuwuhlolo olungahleliwe, olunelebula evulekile olunabantu abangu-266 ababene-metastatic urothelial carcinoma (mUC) kanye nokuguqulwa okuthile kwe-FGFR3. Lezi ziguli zake zathola izindlela zokwelapha ezihlelekile ezingu-1-2, ezihlanganisa i-PD-1 noma i-PD-L1 inhibitor. Ababambiqhaza banikezwe ngokungahleliwe ngesilinganiso esingu-1:1 ukuze bathole i-erdafitinib noma inketho yokwelapha ngamakhemikhali ekhethwa umphenyi, okungaba i-docetaxel noma i-vinflunine. I-stratified randomization yenziwa ngokusekelwe endaweni, isimo sokusebenza, kanye nokuvela kwe-visceral noma i-bone metastases. Ku-75% weziguli elabhorethri emaphakathi, i-therascreen FGFR RGQ RT-PCR kit (Qiagen) ithole ukuguqulwa kwe-FGFR3 kuzicubu zesimila, iziguli ezisele ezinezifundo zendawo zokulandelana kwesizukulwane esilandelayo zithola ukuguqulwa.

Isilinganiso esiyinhloko sokusebenza kwakungukusinda okuphelele (OS). Ukusinda kwe-progression-free survival (PFS) okuhlolwe umphenyi kanye nezinga lokuphendula lenhloso (ORR) bekungamamethrikhi emiphumela engeziwe.

Kube khona ukuthuthuka okuphawulekayo kwezibalo ekusindeni kukonke (i-OS), ukusinda kwe-progression-free (PFS), kanye nezinga lokuphendula lenhloso (ORR) lapho kusetshenziswa i-erdafitinib esikhundleni sokwelashwa ngamakhemikhali. Ukusinda okuphelele okuphakathi kwakuyizinyanga ezingu-12.1 (95% CI: 10.3, 16.4) ezigulini eziphathwe nge-erdafitinib nezinyanga ezingu-7.8 (95% CI: 6.5, 11.1) kulabo abathola i-chemotherapy. Isilinganiso sengozi (HR) sasingu-0.64 (95% CI: 0.47, 0.88) ngevelu engu-p engu-0.0050. Ukusinda okuphakathi kokuqhubekela phambili kwamahhala kwakuyizinyanga ezingu-5.6 (95% CI: 4.4, 5.7) ezigulini eziphathwe nge-erdafitinib kanye nezinyanga ezingu-2.7 (95% CI: 1.8, 3.7) kulabo abathola i-chemotherapy. Isilinganiso sengozi sasingu-0.58 (95% CI: 0.44, 0.78) ngevelu engu-p engu-0.0002. Izinga lokuphendula eliqinisekisiwe (ORR) laliyi-35.3% (95% CI: 27.3, 43.9) ezigulini eziphathwe nge-erdafitinib kanye ne-8.5% (95% CI: 4.3, 14.6) kulabo abathola i-chemotherapy (i-p-value <0.001 ).

Ukusabela okubi kakhulu okuvame kakhulu, okwenzeka ezimweni ezingaphezu kuka-20%, kufaka phakathi amazinga e-phosphate aphakeme, izinkinga zezinzipho, isifo sohudo, ukuvuvukala komlomo, amazinga aphezulu e-alkaline phosphatase, ukwehla kwamazinga e-hemoglobin, amazinga aphezulu e-alanine aminotransferase, amazinga aphezulu e-aspartate aminotransferase, ukunciphisa amazinga e-sodium, ukwanda kwamazinga e-creatinine, umlomo owomile, amazinga e-phosphate ancishisiwe, isimo sesikhumba esithinta izintende namatheni, umuzwa oshintshile wokunambitha, ukukhathala, isikhumba esomile, ukuqunjelwa, ukunciphisa ukudla, ukwanda kwamazinga e-calcium, ukulahlekelwa izinwele, amehlo omile, amazinga aphezulu e-potassium. , nokuncipha kwesisindo.

Umthamo ophakanyisiwe we-erdafitinib ngu-8 mg othathwa ngomlomo kanye ngosuku, ngokunyuka okungaba ku-9 mg kanye ngosuku ngemva kwezinsuku eziyi-14 kuya kwezingu-21 kuye ngokubekezelelana, ikakhulukazi i-hyperphosphatemia. Qhubeka nokwelashwa kuze kube yilapho isifo siba sibi kakhulu noma imiphumela engemihle ingabekezeleleki.