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Lookup NU author(s): Professor Alastair GreystokeORCiD, Professor Ruth Plummer, Dr Christoph OingORCiD, Dr Pasquale RescignoORCiD
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND).
Copyright © 2023. Published by Elsevier B.V. CONTEXT: PARP inhibitors (PARPi) are established treatments for metastatic castration-resistant prostate cancer (mCRPC) with homologous recombination repair (HRR) deficiency after androgen receptor signalling inhibitor (ARSI) failure. New PARPi + ARSI combinations have been tested in all comers, although their clinical relevance in HRR-proficient tumours remains uncertain. OBJECTIVE: To quantitatively synthesise evidence from randomised trials assessing the efficacy and safety of PARPi + ARSI combinations for first-line treatment of mCRPC. EVIDENCE ACQUISITION: We searched the PubMed, EMBASE, SCOPUS, and Cochrane Library databases up to February 28, 2023. Randomised controlled trials (RCTs) comparing PARPi + ARSI versus placebo + ARSI for first-line treatment of mCRPC were eligible. Two reviewers independently performed screening and data extraction and assessed the risk of bias, while a third reviewer evaluated the eligibility criteria. EVIDENCE SYNTHESIS: Overall, three phase 3 RCTs were included in the systematic review: PROPEL, MAGNITUDE, and TALAPRO-2. A total of 2601 patients with mCRPC were enrolled. Two of these trials (PROPEL and TALAPRO-2) assessed the radiographic progression-free survival benefit of PARPi + ARSI for first-line treatment of mCRPC, independent of HRR status. The pooled hazard ratio was 0.62 (95% confidence interval 0.53-0.72). The pooled hazard ratio for overall survival was 0.84 (95% confidence interval 0.72-0.98), indicating a 16% reduction in the risk of death among patients who received the combination. CONCLUSIONS: Results from this meta-analysis support the use of ARSI + PARPi combinations in biomarker-unselected mCRPC. However, such combinations might be less clinically relevant in HRR-proficient cancers, especially considering the change in treatment landscape for mCRPC. PATIENT SUMMARY: We looked at outcomes from trials testing combinations of two classes of drugs (PARP inhibitors and ARSI) in advanced prostate cancer. We found that these combinations seem to work regardless of gene mutations identified as biomarkers of response to PARP inhibitors when used on their own.
Author(s): Messina C, Giunta EF, Signori A, Rebuzzi SE, Banna GL, Maniam A, Buti S, Cattrini C, Fornarini G, Bauckneht M, Greystoke A, Plummer R, Oing C, Rescigno P
Publication type: Article
Publication status: Published
Journal: European Urology Oncology
Year: 2024
Volume: 7
Issue: 2
Pages: 179-188
Print publication date: 01/04/2024
Online publication date: 12/08/2023
Acceptance date: 26/07/2023
Date deposited: 24/07/2024
ISSN (electronic): 2588-9311
Publisher: Elsevier BV
URL: https://doi.org/10.1016/j.euo.2023.07.013
DOI: 10.1016/j.euo.2023.07.013
PubMed id: 37574390
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