Agasti 2023: Inhlanganisela yomthamo ongaguquki we-niraparib ne-abiraterone acetate (Akeega, Janssen Biotech, Inc.), kanye ne-prednisone, kuvunywe i-Food and Drug Administration yeziguli ezikhulile ezinomdlavuza wendlala yesinye (mCRPC) okufakazelwe ukuthi iyingozi noma okusolwa ukuthi iyingozi ngenxa yokuguqulwa kwe-BRCA.
Iqoqo 1 le-MAGNITUDE (NCT03748641), isilingo esilawulwa ngokungahleliwe, esingaboni kabili, esilawulwa yi-placebo esibhalise iziguli ze-423 ezine-homologous recombination repair (HRR) gene-mutated mCRPC, sihlole ukusebenza kokwelashwa. I-Niraparib 200 mg ne-abiraterone acetate 1,000 mg plus prednisone 10 mg nsuku zonke noma i-placebo ne-abiraterone acetate kanye ne-prednisone nsuku zonke zinikezwe iziguli nge-1: 1 randomization. Iziguli kufanele zenze i-orchiectomy esikhathini esedlule noma zibe kuma-analogue e-GnRH. I-Abiraterone acetate kanye ne-prednisone kuze kube yizinyanga ezine esikhathini esidlule, kanye ne-ADT eqhubekayo, kwaba ukuphela kokwelapha okuhleliwe kwangaphambili iziguli ezine-mCRPC ezazifanelekela ukukuthola. Iziguli kungenzeka ukuthi ngaphambilini zithole ukwelashwa okuhlosiwe kwe-docetaxel noma i-androgen-receptor (AR) phakathi nokugula kwazo. I-docetaxel yangaphambili, ukwelashwa okuhlosiwe kwangaphambili kwe-AR, i-abiraterone acetate yangaphambili ene-prednisone, kanye nesimo se-BRCA kwacatshangelwa lapho kuhlelwa i-randomization. Abangu-225 (53%) kubantu abangama-423 ababhalisiwe baba nokuguquguquka kofuzo kwe-BRCA okwakhonjwa kamuva (i-BRCAm). Iziguli ezine-mCRPC ezingazange zibe nokuguqulwa kofuzo lwe-HRR (Iqoqo 2 le-MAGNITUDE) azitholanga nzuzo njengoba isimo sobuze saneliswa.
I-Radiographic progression-free survival (rPFS), enqunywa ukubuyekezwa okuzimele okuphuphuthekile futhi kusekelwe I-prostate Cancer I-Working Group 3 criteria yethambo, kwakuyisilinganiso esiyinhloko somphumela wokusebenza ngempumelelo. Enye inhloso bekungukusinda okuphelele (OS).
Ngezinyanga ezingu-16.6 ezimaphakathi nezinyanga ezingu-10.9, i-niraparib ne-abiraterone acetate kanye ne-prednisone ibonise ukuthuthukiswa okuphawulekayo kwezibalo ku-rPFS uma kuqhathaniswa ne-placebo ne-abiraterone acetate plus prednisone (HR 0.53; 95% CI 0.36, 0.79; p=0.0014). Ezigulini ze-BRCAm, ukuhlaziya kwe-OS kokuhlola kwembule i-median yezinyanga ezingu-30.4 vs. 28.6 (HR 0.79; 95% CI: 0.55, 1.12) evuna ingalo yokuhlola. Nakuba kube nokuthuthuka okuphawulekayo kwezibalo ku-rPFS ku-Cohort 1 ngenhloso yokwelapha (i-ITT) inani labantu abakwa-HRR (HR 0.73; 95% CI 0.56, 0.96; p=0.0217), izilinganiso zezingozi ze-rPFS ne-OS eqenjini elincane lika-198 ( Ama-47%) eziguli ezinezinguquko ze-HRCA okungezona eze-BRCA bezingu-0.99 no-1.13, ngokulandelana, okubonisa ukuthi ukuthuthukiswa kwesibalo sabantu abaguquliwe kofuzo be-ITT HRR kudalwe kakhulu
Ukuncipha kwe-hemoglobin, i-lymphocyte encishisiwe, ukuncipha kwamangqamuzana amhlophe egazi, ubuhlungu bemisipha, ukukhathala, ukuncipha kwamaplatelet, ukwanda kwe-alkaline phosphatase, ukuqunjelwa, umfutho wegazi ophakeme, isicanucanu, ukuncipha kwama-neutrophils, ukwanda kwe-creatinine, ukwanda kwe-potassium, ukwehla kwe-potassium, kanye nokwanda kwe-AST kwaba ukusabela okungathandeki okuvame kakhulu. (20%), kanye nokungajwayelekile kwaselabhorethri. Ku-Cohort 1 ye-MAGNITUDE (n=423), i-27% yeziguli ezine-mCRPC eziphathwa nge-niraparib ne-abiraterone acetate nge-prednisone zidinga ukumpontshelwa igazi, ne-11% edinga ukumpontshelwa okuningi.
Umthamo womlomo wansuku zonke wama-200 mg we-niraparib kanye ne-1,000 mg ye-abiraterone acetate ehlanganiswe no-10 mg we-prednisone welulekwa ku-Akeega kuze kube yilapho isifo siqhubeka noma ubuthi obungabekezeleleki. Iziguli ezisebenzisa i-niraparib, i-abiraterone acetate, ne-prednisone kufanele futhi zithathe i-analogue ye-GnRH ngesikhathi esifanayo, noma bekufanele ngabe zenziwa i-orchiectomy yamazwe amabili.
