Re: Niraparib and Abiraterone Acetate for Metastatic Castration-resistant Prostate Cancer.

Eur Urol

GRC 5 Predictive Onco-Uro, Sorbonne University, Department of Urology, Pitie-Salpetriere Hospital, AP-HP, Paris, France. Electronic address:

Published: January 2024

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http://dx.doi.org/10.1016/j.eururo.2023.09.012DOI Listing

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Metastatic prostate cancer remains incurable. Though significant progress has been made in the field, the search for agents that improve outcomes for patients is ongoing. Several clinical trials have explored the benefit of combining PARP inhibitors (PARPi) with androgen receptor pathway inhibitors (ARPIs) for metastatic castrate resistant prostate cancer (mCRPC), especially those cancers with alterations in homologous recombination repair (HRR) genes.

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Background: Without head-to-head trials between talazoparib+enzalutamide (TALA + ENZA), olaparib+abiraterone acetate (OLAP + AAP), and niraparib plus AAP (NIRA + AAP) the ability to evaluate their relative efficacy as first-line (1 L) treatment in metastatic castration-resistant prostate cancer (mCRPC) is limited. The objective of this study was to assess the relative efficacy between TALA + ENZA (TALAPRO-2) versus OLAP + AAP (PROpel) and NIRA + AAP (MAGNITUDE) in 1 L mCRPC via a matching-adjusted indirect treatment comparison (MAIC).

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Introduction: Niraparib, a PARP1/2 inhibitor, is newly approved in combination with abiraterone acetate (AA) plus prednisone or prednisolone (niraparib/AA+P) for the treatment of adult patients with BRCA-mutated, treatment-naïve metastatic castration resistant prostate cancer (mCRPC). Detailed guidance beyond the prescribing information may be helpful in managing the side effect profile and dosing practicalities of this combination therapy.

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Background And Objective: The phase 3 MAGNITUDE trial assessed the efficacy and safety of niraparib 200 mg and abiraterone acetate 1000 mg plus prednisone 10 mg (AAP) in patients with metastatic castration-resistant prostate cancer (mCRPC) and alterations in homologous recombination repair (HRR) genes. Here we report final analysis results for patient-reported outcomes (PROs) in the HRR cohort with a focus on BRCA1/2 alterations (BRCA).

Methods: Protocol-specified endpoints evaluated patient-reported symptoms, health-related quality of life (HRQoL), and tolerability (side-effect bother) using the Brief Pain Inventory-Short Form (BPI-SF), Functional Assessment of Cancer Therapy-Prostate (FACT-P), and EQ-5D-5L questionnaires.

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Background: MAGNITUDE (NCT03748641) demonstrated favourable outcomes with niraparib plus abiraterone acetate plus prednisone (+AAP) versus placebo+AAP in patients with BRCA1/2-altered metastatic castration-resistant prostate cancer (mCRPC). Imbalances in prognostic variables were reported between arms, which impacts estimation of both the clinical benefit and cost‑effectiveness of niraparib+AAP for healthcare systems. A pre-specified multivariable analysis (MVA) demonstrated improved overall survival (OS) with niraparib+AAP.

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