Niraparib With Abiraterone Acetate and Prednisone for Metastatic Castration-Resistant Prostate Cancer: Results From the Phase 2 Quest Study

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Conference Proceeding

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Journal of Urology



Approximately 20% of metastatic prostate cancers have alterations in genes associated with homologous recombination repair deficiency (HRD). Niraparib (NIRA) is a highly selective polyadenosine diphosphate-ribose polymerase (PARP) inhibitor and abiraterone acetate (AA) inhibits androgen axis signaling, which has a role in DNA repair. Targeting both oncogenic drivers may enhance efficacy in metastatic castration-resistant prostate cancer (mCRPC). The phase 2 QUEST study (NCT03431350) evaluated NIRA combinations in patients (pts) with mCRPC. We report safety, tolerability and efficacy of NIRA with AA + prednisone (AAP).


Pts with mCRPC and alterations in HRD genes with progression on 1 line of next generation AR-targeted therapy received NIRA 200mg once daily + AAP. Primary endpoints were incidence and severity of adverse events (AEs) and composite response rate (CRR), defined as proportion of pts with 1 of the following: objective response, circulating tumor cell (CTC) response, or prostate specific antigen (PSA) decline ≥50% (PSA50). Key secondary endpoints were CTC response rate, objective response rate (ORR), and radiographic progression-free survival (rPFS). Responses are presented with 90% 2-sided confidence intervals (CI); time-to-event endpoints were evaluated by the Kaplan-Meier method.


24 pts were enrolled. 41.7% had soft tissue or nodal metastasis, 29.2% had prior docetaxel. 17 pts had BRCA1/2 alterations, 2 pts each had ATM or CHEK2, 1 each had PALB2 or FANCA. With a median follow-up of 18 mos, 8 pts remain on treatment. Median duration of NIRA was 10.3 mos (range 0.7‒22.0). The most common grade ≥3 AEs were anemia (41.7%), thrombocytopenia (20.8%), fatigue (16.7%), and neutropenia (12.5%). Treatment-emergent AEs (TEAE) led to dose interruption/reduction in 14 (58.3%) pts and discontinuation in 2 pts. There were serious drug-related AEs in 3 pts and no deaths due to AEs. Of 23 pts in the efficacy population (1 pt was HRD-negative), CRR was 52.2% (90% CI, 33.5‒70.4). ORR was 50% (5/10 pts; 90% CI, 9.0–40.4); duration of response was 4.73 mos (range 3.7‒8.2). CTC response rate was 26.1% (90% CI, 12.0–45.1) and PSA50 was 30.4% (90% CI, 15.2‒49.6). Median rPFS was 11.0 mos (90% CI, 9.7‒not estimable).


In pts with mCRPC and HRD alterations and prior AR-targeted therapy, NIRA+AAP has promising efficacy and a manageable safety profile. The phase 3 MAGNITUDE study further evaluates this combination in pts with newly diagnosed mCRPC.




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American Urological Association Annual Meeting, May 13-16, 2022, New Orleans, LA.