I-Janssen Pharmaceutical Companies of Johnson & Johnson namuhla imemezele imiphumela yokuqala evela ocwaningweni lweSigaba 3 MAGNITUDE oluhlola ukusetshenziswa kophenyo kwe-niraparib, i-poly-ADP ribose polymerase (PARP) inhibitor ekhethiwe, ihlanganiswe ne-abiraterone acetate kanye ne-prednisone ezigulini ezine-metastatic castration- ukumelana nomdlavuza wendlala yesinye (mCRPC) noma ngaphandle kwezinguquko ezithile zofuzo zokulungisa i-homologous recombination (HRR). Ekuhlaziyweni kokugcina kokusinda kwe-radiographic progression-free (rPFS), inhlanganisela yokwelapha ye-niraparib ne-abiraterone acetate kanye ne-prednisone ibonise ukuthuthuka okuphawulekayo kwezibalo ezigulini ezinokushintshwa kofuzo lwe-HRR. Imiphumela izofakwa kuphrezentheshini yomlomo ephuke sekwephuzile (Abstract #12; Oral Abstract Session A) e-American Society of Clinical Oncology's Genitourinary (ASCO GU) Cancers Symposium, ezokwenzeka e-San Francisco futhi cishe kusukela ngo-February 17-19, 2022 .

I-MAGNITUDE (NCT03748641) iyiSigaba 3, esingahleliwe, esingaboni kabili, esilawulwa yi-placebo, isifundo se-multicenter esihlola ukuphepha nokusebenza kahle kwenhlanganisela ye-niraparib ne-abiraterone acetate kanye ne-prednisone njengendlela yokwelapha yomugqa wokuqala ezigulini ezine-mCRPC. Ucwaningo lwe-MAGNITUDE lwaklanywa ngenhloso namaqoqo amabili azimele ukuze kuhlolwe umphumela wokwelashwa ezigulini ezinezinguquko zofuzo ze-HRR nezingenazo (okuhlanganisa i-ATM, BRCA1, BRCA2, BRIP1, CDK12, CHEK2, FANCA, HDAC2, PALB2 izinguquko) ngokuqhathaniswa nezinga lokunakekelwa. Iqembu leziguli ezinezinguquko zezakhi zofuzo ze-HRR okungenzeka zihlonzwe zabhalisa iziguli ze-423, neziguli ezingahleliwe ukuze zithole inhlanganisela ye-niraparib ne-abiraterone acetate kanye ne-prednisone (ingalo ehlanganisiwe [n = 212]) noma i-placebo ne-abiraterone acetate kanye ne-prednisone (ingalo yokulawula [n] =211]). Ekulandeleni okumaphakathi kwezinyanga eziyi-18.6, iziguli ezisengalweni yenhlanganisela yeqembu elinezinguquko zofuzo ze-HRR zibonise ukuthuthuka okukhulu ku-rPFS, ngokuncipha kwengozi yokuqhubeka noma yokufa ngamaphesenti angama-27 (isilinganiso sengozi [HR] 0.73; p =0.022). Lokhu kuthuthukiswa kwagqama kakhulu ezigulini ezinezinguquko zofuzo ze-BRCA1/2, lapho ukuncipha kwengozi okungamaphesenti angu-47 kwaqashelwa i-rPFS (HR 0.53; p=0.001), njengoba kuhlaziywa ngokubuyekezwa okumaphakathi okuzimele okuphuphuthekile (BICR). Ukuthuthukiswa okungaguquguquki kodwa okukhulu kubonwe ku-rPFS ehlolwe umphenyi, ebonise ukuncipha kwengozi okungamaphesenti angama-36 ezigulini ezinokuguqulwa kwezakhi zofuzo ze-HRR (HR: 0.64; p=0.002), kanye nokunciphisa ubungozi ngamaphesenti angama-50 ezigulini ezinofuzo lwe-BRCA1/2 izinguquko (HR: 0.50; p=0.0006).

Iqembu elingenazo izinguquko zofuzo ze-HRR (n=233) lihlangabezane nenqubo echazwe ngaphambilini eyize ngo-Agasti 2020, engabonisi nzuzo kusukela kunhlanganisela yokwelashwa (HR>1) ku-HRR biomarker negative. Ukubhalisa kuleli qoqo kuye kwamiswa ngesikhathi sokungasebenzi ngesincomo seKomidi Elizimele Lokuqapha Idatha. Abaphenyi neziguli bebengaphuphuthekisiwe futhi banikezwe ithuba lokuqhubeka nokwelashwa nge-niraparib ne-abiraterone acetate kanye ne-prednisone noma bathole i-abiraterone acetate kanye ne-prednisone kuphela ngokubona komseshi wocwaningo.

Ezigulini ezinokushintshwa kwezakhi zofuzo ze-HRR, ukuthuthukiswa okuhlobene nomtholampilo emiphumeleni nakho kwabonakala kulokhu kuhlaziywa kwesikhashana kokuqala kweziphetho zesibili okuhlanganisa isikhathi sokuqalwa kwe-cytotoxic chemotherapy, isikhathi sokuqhubekela phambili kwezimpawu kanye nesikhathi sokuqhubekela phambili kwe-PSA. Ukwengeza, izinga lokuphendula elihlosiwe liye lathuthukiswa ngokuhlanganiswa kwe-niraparib ne-abiraterone acetate kanye ne-prednisone. Sekukonke idatha yokusinda ibingakavuthwa kulokhu kuhlaziywa kwesikhashana futhi ukulandelelwa kuzoqhubeka kuzo zonke izindawo zokugcina.

Iphrofayili yokuphepha eqashiwe yenhlanganisela ye-niraparib ne-abiraterone acetate plus prednisone yayihambisana nephrofayili yokuphepha eyaziwayo ye-ejenti ngayinye. Ezigulini ezinokuguqulwa kwezakhi zofuzo zakwa-HRR, amaphesenti angama-67 ahlangabezana nezimo ezingezinhle zeBanga lesi-3 (AEs) kanti amaphesenti angama-46.4 athola ama-AE eBanga lesi-4, eshukunyiswa kakhulu yi-anemia nokukhathala. Amazinga okuyekwa kwengalo ehlanganisiwe nengalo yokulawula ayengamaphesenti angu-10.8 namaphesenti angu-4.7 ngokulandelana. Inhlanganisela ye-niraparib ne-abiraterone acetate kanye ne-prednisone iphinde yagcina ikhwalithi yokuphila iyonke uma iqhathaniswa ne-placebo ne-abiraterone acetate kanye ne-prednisone njengoba kulinganiswa esikalini sokuhlolwa okusebenzayo kwe-Cancer Therapy-Prostate (FACT-P).

Iziguli ezinokushintshwa kofuzo lwe-HRR, njenge-BRCA1/2, zisengozini eyengeziwe yokuba nomdlavuza wendlala yesinye, futhi umdlavuza wendlala yesinye ohlobene ne-BRCA uvame ukuba nolaka. Ukuphila isikhathi eside kuphansi ezigulini ezine-mCRPC futhi lezo ezinokuguqulwa kwezakhi zofuzo ze-HRR zibhekana nesimo esibi kakhulu sokubikezela, okwenza kube nesidingo esibalulekile sezokwelapha esingahlangatshezwanga sezindlela zokwelapha ezintsha kulesi sifo.

LOKHO ONGAKUTHATHE KULESI SIHLOKO:

6-month median follow-up, patients in the combination arm of the cohort with HRR gene alterations showed a significant improvement in rPFS, with a reduction in the risk of progression or death of 27 percent (hazard ratio [HR] 0.
The cohort of patients with prospectively-identified HRR gene alterations enrolled 423 patients, with patients randomized to receive the combination of niraparib and abiraterone acetate plus prednisone (combination arm [n=212]) or placebo and abiraterone acetate plus prednisone (control arm [n=211]).
MAGNITUDE (NCT03748641) is a Phase 3, randomized, double-blind, placebo-controlled, multicenter study evaluating the safety and efficacy of the combination of niraparib and abiraterone acetate plus prednisone as a first-line therapy in patients with mCRPC.