Luulyo 2023: Maamulka Cuntada iyo Dawooyinka ayaa ka nadiifiyay talazoparib (Talzenna, Pfizer, Inc.) enzalutamide loogu talagalay hagaajinta dib-u-habaynta dib-u-habaynta hidda-wadaha (HRR) ee kansarka qanjirka 'prostate' (mCRPC).
TALAPRO-2 (NCT03395197), a randomised, double-blind, placebo-controlled, multi-cohort study with 399 patients with HRR gene-mutated mCRPC, looked at how well the drug worked. The patients were given either enzalutamide 160 mg daily plus talazoparib 0.5 mg daily or a dummy every day. Patients had to get an orchiectomy first, and if that didn’t happen, they were given gonadotropin-releasing hormone (GnRH) analogues. Patients who had received systemic treatment for mCRPC before were not allowed, but patients who had received CYP17 inhibitors or docetaxel before for metastatic castration-sensitive kansarka qanjirka 'prostate (mCSPC) were allowed. Prior treatment with a CYP17 inhibitor or docetaxel changed how the randomization was done. HRR genes (ATM, ATR, BRCA1, BRCA2, CDK12, CHEK2, FANCA, MLH1, MRE11A, NBN, PALB2, or RAD51C) were looked at using next-generation sequencing tests based on tumour tissue and/or circulating tumour DNA (ctDNA).
Horumarka shucaaca-la'aanta badbaadada (rPFS) marka loo eego nooca RECIST 1.1 ee unugyada jilicsan iyo kuwa ka shaqeeya kansarka qanjirka 'prostate' heerarka 3 ee lafaha ayaa ahaa cabbirka ugu muhiimsan ee waxtarka. Tan waxa sameeyay indho-la'aan, dib u eegis dhexe oo madax banaan.
Kooxda HRR-ga beddelatay, talazoparib oo leh enzalutamide waxay muujisay horumar la taaban karo oo ku yimid rPFS marka la barbar dhigo placebo oo leh enzalutamide, oo leh dhexdhexaad aan la gaarin bilaha 13.8 (HR 0.45; 95% CI: 0.33, 0.61; p0.0001) . Daraasad cilmi baaris ah oo ay samaysay heerka isbeddelka BRCA, saamiga khatarta ah ee rPFS ee bukaannada leh BRCA-mutated mCRPC (n=155) waxay ahayd 0.20 (95% CI: 0.11-0.36) iyo bukaannada aan BRCAm HRR hidde-mutated mCRPC, wuxuu ahaa 0.72 (0.49-1.07).
Isbeddellada shaybaarka iyo dhibaatooyinka soo raaca ee dhacay in ka badan 10% waqtiga ayaa ahaa daal, hoos u dhaca platelets, hoos u dhaca kalsiyum, lallabbo, rabitaanka cuntada oo hoos u dhaca, hoos u dhaca soodhiyamka, hoos u dhaca fosfatka, jabka, hoos u dhaca magnesium, dawakhaad, bilirubin kordhay, hoos u dhaca potassium, iyo dysgeusia. Dhammaan bukaannada 511 ee qaba mCRPC ee lagu daweeyay talazoparib iyo enzalutamide ee TALAPRO-2 waxay u baahdeen dhiig ku shubid, iyadoo 22% ay u baahan yihiin in ka badan hal. Laba bukaan ayaa laga helay cudurka 'myelodysplastic syndrome'/acute myeloid leukemia (MDS/AML).
Qiyaasta talazoparib ee la soo jeediyay waa 0.5 mg oo afka laga qaato hal mar maalintii iyadoo la isticmaalayo enzalutamide ilaa uu cudurku ka sii darayo ama waxyeelada ay leedahay aad u xun. Enzalutamide waa in afka laga qaataa hal mar maalintii oo qadarkeedu yahay 160 mg. Bukaannada qaatay talazoparib iyo enzalutamide waa in sidoo kale ay qaataan analoogga GnRH ama laga saaro labadaba xiniinyaha.
U fiirso macluumaadka dhamaystiran ee Talzenna
