July 2023: Chikafu neDrug Administration yakabvisa talazoparib (Talzenna, Pfizer, Inc.) ne enzalutamide ye homologous recombination repair (HRR) gene mutations mune metastatic castration-resistant prostate cancer (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 Kenza yeprotate (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).
Radiographic progression-free survival (rPFS) maererano neRECIST vhezheni 1.1 yematishu akapfava uye Prostate Cancer Working Boka 3 zviyero zvebhonzo ndiyo yaive yakanyanya kukosha chiyero chekushanda. Izvi zvakaitwa nekupofumadzwa, yakazvimirira central wongororo.
Muboka reHRR gene-mutated, talazoparib ine enzalutamide yakaratidza kuvandudzika kwakakosha murPFS zvichienzaniswa neplacebo ine enzalutamide, ine midhinha isingasviki vs. 13.8 mwedzi (HR 0.45; 95% CI: 0.33, 0.61; p0.0001). Muchidzidzo chekuongorora neBRCA mutation status, chiyero chehazard ye rPFS muvarwere vane BRCA-mutated mCRPC (n = 155) yaiva 0.20 (95% CI: 0.11-0.36) uye kune varwere vasina-BRCAm HRR gene-mutated mCRPC, yaiva 0.72-0.49.
Laboratory abnormalities nemigumisiro yechirwere yakaitika kupfuura 10% yenguva yacho kwaiva kuneta, kuderera kweplatelet, kuderera kwecalcium, kusvotwa, kuderera kwechido, kuderera kwesodium, kuderera kwephosphate, kuputsika, kuderera kwemagnesium, dzungu, kuwedzera bilirubin, kuderedza potassium, uye dysgeusia. Vese varwere mazana mashanu nerimwe vane mCRPC vakarapwa netalazoparib uye enzalutamide paTALAPRO-511 vaida kuwedzerwa ropa, 2% ichida rinopfuura rimwechete. Varwere vaviri vakawanikwa vaine myelodysplastic syndrome/acute myeloid leukemia (MDS/AML).
Muyero unofungidzirwa wetalazoparib ndeye 0.5 mg inotorwa nemuromo kamwe chete pazuva ne enzalutamide kusvika chirwere chanyanya kuipa kana mhedzisiro yanyanya kuipa. Enzalutamide inofanira kutorwa nemuromo kamwe chete pazuva pahuwandu hwe160 mg. Varwere vakatora talazoparib uye enzalutamide vaifanira kunge vatorawo analogue yeGnRH kana kubviswa machende avo ese.
Wona ruzivo rwakazara rwekutemerwa kweTalzenna
