August 2023: Isku darka qiyaasta go'an ee niraparib iyo abiraterone acetate (Akeega, Janssen Biotech, Inc.), oo ay weheliso prednisone, waxaa ansixiyay Maamulka Cuntada iyo Dawooyinka ee bukaanka qaangaarka ah ee qaba kansarka qanjirka 'prostate' (mCRPC) kaas oo la xaqiijiyay inuu yahay waxyeello ama looga shakisan yahay inay waxyeello leedahay sababtoo ah isbeddelka BRCA.
Kooxda 1 ee MAGNITUDE (NCT03748641), tijaabo aan kala sooc lahayn, laba-indho la'aan, tijaabo la xakameynayo placebo oo diiwaan gashan 423 bukaan oo leh dib-u-hagaajinta dib-u-habaynta isku-dhafka ah (HRR) mCRPC, ayaa baadhay waxtarka daaweynta. Niraparib 200 mg iyo abiraterone acetate 1,000 mg oo lagu daray prednisone 10 mg maalin kasta ama placebo iyo abiraterone acetate oo lagu daray prednisone maalin kasta ayaa la siiyay bukaanada 1: 1 randomization. Bukaan-socodka waa in ay hore u mareen orchiectomy ama waa in ay qaataan analogues GnRH. Abiraterone acetate iyo prednisone ilaa afar bilood oo la soo dhaafay, oo ay weheliso ADT joogto ah, ayaa ahayd daawaynta nidaamsan ee kaliya ee hore ee bukaannada qaba mCRPC ay u qalmeen. Bukaan-socodka ayaa laga yaabaa in ay hore u heleen daawaynta la bar tilmaameedsan yahay docetaxel ama androgen-receptor (AR). Docetaxel ka hor, daawaynta bartilmaameedka hore ee AR, ka hor abiraterone acetate oo leh prednisone, iyo heerka BRCA ayaa la tixgeliyey marka la qeexayo kala-soocidda. 225 (53%) ee 423 qofood ee la diiwaan galiyay waxay lahaayeen isku-bedelka hidda-wadaha BRCA oo markii dambe la aqoonsaday (BRCAm). Bukaannada qaba mCRPC ee aan lahayn beddelka hidda-wadaha HRR (Kooxda 2 ee MAGNITUDE) ma aysan helin wax faa'iido ah tan iyo markii xaaladda wax-tarnimada la qanciyay.
Badbaadada-horumar-la'aanta shucaaca (rPFS), oo ay go'aamisay indha-indhayn madax-bannaanida dhexe oo ku salaysan Cancer Prostate Kooxda shaqada 3 shuruudaha lafaha, waxay ahayd qiyaasta natiijada waxtarka aasaasiga ah. Ujeedada kale waxay ahayd badbaadada guud (OS).
Dhexdhexaadinta bilaha 16.6 vs. 10.9 bilood, niraparib iyo abiraterone acetate oo lagu daray prednisone waxay muujisay horumar la taaban karo oo ku yimid rPFS marka la barbardhigo placebo iyo abiraterone acetate iyo prednisone (HR 0.53; 95% CI 0.36, 0.79; p0.0014) . Bukaannada BRCAm, falanqaynta OS-da ee sahaminta ayaa shaaca ka qaaday dhexdhexaadinta 30.4 vs. 28.6 bilood (HR 0.79; 95% CI: 0.55, 1.12) oo door bidaaya cududda tijaabada ah. Iyadoo ay jirto horumar la taaban karo oo ku yimid rPFS kooxda 1 ujeedka lagu daweynayo (ITT) dadka HRR (HR 0.73; 95% CI 0.56, 0.96; p=0.0217), saamiga halista ee rPFS iyo OS ee kooxda hoose ee 198 ( 47%) bukaanada qaba isbeddellada HRR ee aan BRCA ahayn waxay ahaayeen 0.99 iyo 1.13, siday u kala horreeyaan, taasoo muujinaysa in horumarka ITT HRR-ga dadka is beddellay ay ugu horrayn sabab u tahay
Haemoglobin-ka oo yaraada, lymphocytes oo yaraada, unugyada dhiiga cad oo yaraada, xanuunka murqaha, daal, platelets oo yaraada, fosfatase alkaline oo kordha, calool istaaga, dhiig karka, lallabbo, neutrophils oo yaraada, creatinine oo kordhay, potassium oo kordhay, potassium oo yaraada, iyo AST oo kordhay ayaa ahaa falcelinta ugu badan (20%), oo ay la socdaan cilladaha shaybaadhka. Kooxda 1 ee MAGNITUDE (n=423), 27% bukaanada qaba mCRPC ee lagu daweeyay niraparib iyo abiraterone acetate oo leh prednisone waxay u baahdeen dhiig ku shubid, iyadoo 11% ay u baahan tahay ku shubid badan.
Qiyaasta afka ee maalinlaha ah ee 200 mg of niraparib iyo 1,000 mg abiraterone acetate oo lagu daray 10 mg of prednisone ayaa lagula talinayaa Akeega ilaa uu cudurku ka sii socdo ama sunta aan loo dulqaadan karin. Bukaannada isticmaalaya niraparib, abiraterone acetate, iyo prednisone waa inay sidoo kale qaataan analoogga GnRH isku mar, ama waa inay maraan orchiectomy laba geesood ah.
