AUA 2022: Niraparib with Abiraterone Acetate and Prednisone for Metastatic Castration-Resistant Prostate Cancer: Results from the Phase 2 QUEST Study

(UroToday.com) In a moderated poster presentation at the 2022 American Urologic Association Annual Meeting held in New Orleans and virtually, Dr. Tutrone presented results of the phase 2 QUEST study examining the role of combination therapy with niraparib and abiraterone acetate and prednisone in metastatic castration resistant prostate cancer (mCRPC). Approximately 20% of patients with metastatic prostate cancer will have alterations in genes associated with homologous recombination repair deficiency (HRD) which may sensitize to polyadenosine diphosphate-ribose polymerase (PARP) inhibition. Niraparib is a highly selective PARP inhibitor. Abiraterone acetate (AA) is a standard of care treatment approach in mCRPC which acts through inhibition of androgen axis signaling, which has a role in DNA repair. Targeting both of these pathways may enhance efficacy in metastatic castration-resistant prostate cancer (mCRPC), a hypothesis tested in the phase 2 QUEST study (NCT03431350). In this study, Dr. Tutrone reported safety, tolerability and efficacy results of the combination of niraparib with AA + prednisone (AAP).


This trial enrolled patients with mCRPC and alterations in HRD genes who had evidence of progression on one line of next generation AR-targeted therapy. All patients received niraparib 200mg once daily + AAP. Patients were divided into three cohorts on the basis of the HRD alterations.

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The primary study endpoints were the incidence and severity of adverse events (AEs) and composite response rate (CRR), defined as proportion of patients with at least one of the following: objective response, circulating tumor cell (CTC) response, or prostate specific antigen (PSA) decline ≥50% (PSA50). Further, the authors considered key secondary endpoints including CTC response rate, objective response rate (ORR), and radiographic progression-free survival (rPFS). The response rates are presented with 90% 2-sided confidence intervals (CI) while time-to-event endpoints were evaluated by the Kaplan-Meier method.

The authors included 24 patients of whom 41.7% had soft tissue or nodal metastasis and 29.2% had received prior docetaxel. Of the 24 patients (all who had to have HRD alterations), 17 had BRCA1/2 alterations, 2 each had ATM or CHEK2, and 1 each had PALB2 or FANCA alterations. Over a median follow-up of 18 months, 8 of 24 patients (33%) remain on treatment. The median duration of niraparib therapy was 10.3 months (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%).

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Treatment-emergent AEs (TEAE) led to dose interruption/reduction in 14 (58.3%) patients and discontinuation in 2 patients. Serious drug-related AEs occurred in 3 patients though no deaths due to AEs were observed. Among 23 patients included in the efficacy population (1 patient was excluded as they were HRD-negative), the composite response rate was 52.2% (90% CI, 33.5‒70.4) and objective response rate was 50% (5/10 patients; 90% CI, 9.0–40.4). Among responders, the duration of response was 4.73 months (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).

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The median rPFS was 11.0 months (90% CI, 9.7‒not estimable).

The authors concluded that among patients with mCRPC and HRD alterations who had previously received AR-targeted therapy the combination of niraparib and abiraterone acetate shows promising efficacy and manageable toxicity. Thus, these data formed the basis of the phase 3 MAGNITUDE study which further evaluates this combination as first-line therapy in patients with newly diagnosed mCRPC.

Presented by: Ronald F. Tutrone, MD, Director of Research, Chesapeake Urology Research Associates

Written by: Christopher J.D. Wallis, University of Toronto Twitter: @WallisCJD during the 2022 American Urological Association (AUA) Annual Meeting, New Orleans, LA, Fri, May 13 – Mon, May 16, 2022.

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