Julayi 2023: I-Food and Drug Administration yasula i-talazoparib (Talzenna, Pfizer, Inc.) nge- enzalutamide yokuguqulwa kofuzo lokulungisa kabusha i-homologous recombination (HRR) kumdlavuza wendlala yesinye we-metastatic castration-resistant (mCRPC).
I-TALAPRO-2 (NCT03395197), ucwaningo olungahleliwe, olungaboni kabili, olulawulwa yi-placebo, oluhlanganisa amaqembu amaningi neziguli ezingama-399 ezine-HRR gene-mutated mCRPC, lubheke ukuthi umuthi usebenze kahle kangakanani. Iziguli zanikezwa i- enzalutamide 160 mg nsuku zonke kanye ne-talazoparib 0.5 mg nsuku zonke noma i-dummy nsuku zonke. Iziguli kwadingeka zithole i-orchiectomy kuqala, futhi uma lokho kungenzeki, zanikezwa ama-analogue e-gonadotropin-releasing hormone (GnRH). Iziguli ezake zithole ukwelashwa okuhleliwe kwe-mCRPC ngaphambili azivunyelwe, kodwa iziguli ezake zithole i-CYP17 inhibitors noma i-docetaxel ngaphambilini ngenxa yokuzwela ukuthenwa kwe-metastatic. umdlavuza wendlala (mCSPC) bavunyelwe. Ukwelashwa kwangaphambilini nge-CYP17 inhibitor noma i-docetaxel kushintshe indlela i-randomization eyenziwa ngayo. Izakhi zofuzo ze-HRR (i-ATM, ATR, BRCA1, BRCA2, CDK12, CHEK2, FANCA, MLH1, MRE11A, NBN, PALB2, noma i-RAD51C) zibhekwe kusetshenziswa izivivinyo zokulandelana zesizukulwane esilandelayo ngokusekelwe esiculweni sesimila kanye/noma i-DNA yesimila esijikelezayo (ctDNA) .
Ukusinda kwe-Radiographic progression-free survival (rPFS) ngokwenguqulo ye-RECIST 1.1 yezicubu ezithambile kanye namazinga e-Prostate Cancer Working Group 3 yethambo kwakuyisilinganiso esibaluleke kakhulu sokusebenza. Lokhu kwenziwa ngokubuyekezwa okuphakathi okuphuphuthekile, okuzimele.
Eqenjini le-HRR eliguqulwe izakhi zofuzo, i-talazoparib ene- enzalutamide ibonise ukuthuthuka okuphawulekayo kwezibalo ku-rPFS uma kuqhathaniswa ne-placebo ene enzalutamide, ene-median engafinyelelwanga uma iqhathaniswa nezinyanga ezingu-13.8 (HR 0.45; 95% CI: 0.33, 0.61; p0.0001). Ocwaningweni lokuhlola ngesimo soguquko se-BRCA, isilinganiso sengozi ye-rPFS ezigulini ezine-BRCA-mutated mCRPC (n=155) sasingu-0.20 (95% CI: 0.11–0.36) futhi ezigulini ezine-non-BRCAm HRR gene-mutated mCRPC, kwaba ngu-0.72.
Ukungajwayelekile kwelabhorethri kanye nemiphumela engemihle eyenzeka ngaphezu kwe-10% yesikhathi kwakuwukukhathala, ukwehla kwamaplatelet, ukuncipha kwe-calcium, isicanucanu, ukuncipha kwesifiso sokudla, ukwehla kwe-sodium, ukwehla kwe-phosphate, ukuphuka, ukwehla kwe-magnesium, isiyezi, ukwanda kwe-bilirubin, ukwehla kwe-potassium, ne-dysgeusia. Zonke iziguli ezingu-511 ezine-mCRPC ezalashwa nge-talazoparib kanye ne- enzalutamide ku-TALAPRO-2 zazidinga ukumpontshelwa igazi, kanti u-22% wawudinga okungaphezu kwelilodwa. Iziguli ezimbili zitholwe zine-myelodysplastic syndrome/acute myeloid leukemia (MDS/AML).
Umthamo ophakanyisiwe we-talazoparib ngu-0.5 mg ophuzwa ngomlomo kanye ngosuku nge enzalutamide kuze kube yilapho isifo siba sibi kakhulu noma imiphumela engemihle ibe mibi kakhulu. I-Enzalutamide kufanele iphuzwe ngomlomo kanye ngosuku ngenani elingu-160 mg. Iziguli ezithathe i-talazoparib ne- enzalutamide kwakufanele ngabe zithathe i-analogue ye-GnRH noma zikhishwe womabili amasende azo.
Buka imininingwane egcwele ye-Talzenna
