August 2023: Iyo yakatarwa dosi musanganiswa weniraparib uye abiraterone acetate (Akeega, Janssen Biotech, Inc.), pamwe neprednisone, yakabvumidzwa neFood and Drug Administration yevarwere vakuru vane castration-resistant cancer cancer (mCRPC) yakaratidza kuve zvinokuvadza kana zvinofungidzirwa kuti zvinokuvadza nekuda kwekuchinja kweBRCA.
Cohort 1 ye MAGNITUDE (NCT03748641), muedzo we randomised, double-blind, placebo-controlled controlled test iyo yakanyora varwere ve423 vane homologous recombination repair (HRR) gene-mutated mCRPC, yakaongorora kushanda kwekurapa. Niraparib 200 mg uye abiraterone acetate 1,000 mg pamwe ne prednisone 10 mg zuva nezuva kana placebo uye abiraterone acetate pamwe ne prednisone zuva nezuva zvakapiwa kuvarwere mu1: 1 randomization. Varwere vanofanira kunge vakamboitwa orchiectomy munguva yakapfuura kana kuve paGnRH analogues. Abiraterone acetate plus prednisone kwemwedzi mina yapfuura, pamwe chete neADT inopfuurira, ndiyo chete yekutanga systemic therapy iyo varwere vane mCRPC vaikwanisa. Varwere vanogona kunge vakambogamuchira docetaxel kana androgen-receptor (AR) yakanangwa marapirwo panguva yekurwara kwavo. Pamberi pedocetaxel, yekutanga AR yakanangwa kurapwa, isati yasvika abiraterone acetate ine prednisone, uye chimiro cheBRCA chakatorwa mufungwa pakugadzirisa randomisation. 225 (53%) ye423 vanhu vakanyoreswa vaive neBRCA gene mutations dzakazoonekwa (BRCAm). Varwere vane mCRPC vakanga vasina HRR gene mutation (Cohort 2 ye MAGNITUDE) havana kuwana chero rubatsiro sezvo mamiriro asina maturo akagutsikana.
Radiographic progression-free survival (rPFS), determined by blinded independent central review and based on Prostate Cancer Working Group 3 criteria for bone, was the primary effectiveness outcome measure. Another objective was overall survival (OS).
Nepakati pemwedzi ye16.6 vs. 10.9 mwedzi, niraparib uye abiraterone acetate pamwe ne prednisone yakaratidza kuwedzera kwenhamba mu rPFS kana ichienzaniswa ne placebo uye abiraterone acetate plus prednisone (HR 0.53; 95% CI 0.36, 0.79; p = 0.0014). Muvarwere veBRCAm, kuongororwa kweOs kuongororwa kwakaratidza pakati pe30.4 vs. 28.6 mwedzi (HR 0.79; 95% CI: 0.55, 1.12) mukufarira ruoko rwekuedza. Nepo paive nekuvandudzwa kwakakosha murPFS muCohort 1 chinangwa chekurapa (ITT) HRR huwandu (HR 0.73; 95% CI 0.56, 0.96; p=0.0217), iyo njodzi ratios yerPFS uye OS muchikamu che198 ( 47%) varwere vasina-BRCA HRR mutations vaive 0.99 uye 1.13, zvichiteerana, zvichiratidza kuti kuvandudzwa kweiyo ITT HRR gene-mutated huwandu hwakanyanya kukonzerwa
Yakaderedzwa haemoglobin, yakaderedzwa lymphocytes, kuderedza masero machena eropa, musculoskeletal kurwadziwa, kuneta, kuderera kweplatelet, kuwedzera alkaline phosphatase, kuvimbiswa, hypertension, kusvotwa, kuderedzwa neutrophils, kuwedzera creatinine, yakawedzera potassium, yakaderera potassium, uye kuwedzera AST ndiyo yaiwanzogara yakashata maitiro. (20%), pamwe chete neabnormalities murabhoritari. MuCohort 1 ye MAGNITUDE (n = 423), 27% yevarwere vane mCRPC vanobatwa ne niraparib uye abiraterone acetate ne prednisone yaida kuwedzerwa ropa, uye 11% inoda kuwedzerwa ropa kakawanda.
Mushonga wezuva nezuva we200 mg we niraparib uye 1,000 mg ye abiraterone acetate yakasanganiswa ne 10 mg ye prednisone inorayirwa kuAkeega kusvikira kufambira mberi kwechirwere kana kutyisa kusingagoneki. Varwere vanoshandisa niraparib, abiraterone acetate, uye prednisone vanofanirawo kutora analogue yeGnRH panguva imwe chete, kana kuti vanofanira kunge vakamboitwa bilateral orchiectomy.
