2023 Juli: Administrasi Pangan sareng Narkoba ngabersihkeun talazoparib (Talzenna, Pfizer, Inc.) sareng enzalutamide pikeun mutasi gen homologous recombination (HRR) dina kanker prostat tahan castration metastatik (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 kanker prostat (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) numutkeun RECIST versi 1.1 pikeun jaringan lemes sareng standar Grup Gawé Kanker Prostat 3 pikeun tulang mangrupikeun ukuran efektivitas anu paling penting. Hal ieu dilakukeun ku hiji buta, review sentral bebas.
Dina grup HRR gén-mutated, talazoparib kalawan enzalutamide némbongkeun pamutahiran signifikan sacara statistik dina rPFS dibandingkeun placebo kalawan enzalutamide, kalawan median teu ngahontal vs 13.8 bulan (HR 0.45; 95% CI: 0.33, 0.61; p0.0001) . Dina ulikan éksplorasi ku status mutasi BRCA, rasio bahya pikeun rPFS di penderita BRCA-mutated mCRPC (n = 155) éta 0.20 (95% CI: 0.11-0.36) jeung di penderita non-BRCAm HRR gen-mutated mCRPC, éta 0.72 (0.49-1.07).
Abnormalitas laboratorium sareng efek samping anu kajantenan langkung ti 10% waktos nyaéta kacapean, turun trombosit, turun kalsium, seueul, turun napsu, turun natrium, turun fosfat, patah tulang, turun magnesium, pusing, ningkat bilirubin, turun kalium, sareng dysgeusia. Sadaya 511 pasien kalayan mCRPC anu dirawat kalayan talazoparib sareng enzalutamide dina TALAPRO-2 peryogi transfusi getih, sareng 22% peryogi langkung ti hiji. Dua pasien kapanggih sareng sindrom myelodysplastic / leukemia myeloid akut (MDS / AML).
Dosis talazoparib anu disarankeun nyaéta 0.5 mg oral sakali sadinten sareng enzalutamide dugi ka panyakit janten parah atanapi efek samping parah teuing. Enzalutamide kedah dicandak sacara lisan sakali sapoé dina jumlah 160 mg. Pasién anu nyandak talazoparib sareng enzalutamide kedahna ogé nyandak analog GnRH atanapi nyandak kadua testisna.
Ningali inpormasi resep lengkep pikeun Talzenna
