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Cited by 39Prostate Cancer Treatment and ResearchPARP inhibition in cancer therapyAdvanced Breast Cancer Therapies

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Combining PARP Inhibitors and Androgen Receptor Signalling Inhibitors in Metastatic Prostate Cancer: A Quantitative Synthesis and Meta-analysis

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Messina, Carlo, Giunta, Emilio Francesco, Signori, Alessio, Rebuzzi, Sara Elena, Banna, Giuseppe Luigi, Maniam, Akash, Buti, Sebastiano, Cattrini, Carlo, Fornarini, Giuseppe, Bauckneht, Matteo, Greystoke, Alastair, Plummer, Ruth, Oing, Christoph, Rescigno, Pasquale·2024·European Urology Oncology
DOI 10.1016/j.euo.2023.07.013
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Abstract

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.

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  • In a meta-analysis of the PROpel, TALAPRO-2, and MAGNITUDE trials investigating PARP inhibitor plus ARPI combinations versus placebo plus ARPI in first-line mCRPC, the pooled HRs were 0.62 (95% CI 0.53-0.72) for rPFS and 0.84 (95% CI 0.72-0.98) for OS.

    “In a meta-analysis of the PROpel, TALAPRO-2, and MAGNITUDE trials investigating PARP inhibitor plus ARPI combinations vs placebo plus ARPI in first-line mCRPC, the pooled HRs were 0.62 (95% CI 0.53–0.72) for rPFS, and 0.84 (95% CI 0.72–0.98) for OS [4].”

    From Navigating therapeutic sequencing in the metastatic castration-resistant prostate cancer patient journey (2025) · cites this paper as [4]

  • The meta-analysis suggests a benefit from PARP inhibitor plus ARPI combination in HRR-unselected mCRPC, as PROpel and TALAPRO-2 assessed rPFS independent of HRR status.

    “This suggests a benefit from the combination in HRR-unselected mCRPC, as PROpel and TALAPRO-2 assessed rPFS independent of HRR status [4].”

    From Navigating therapeutic sequencing in the metastatic castration-resistant prostate cancer patient journey (2025) · cites this paper as [4]

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References 32 · Cited by 39

Research works printed but not linked: 31

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Metadata

Authors
Messina, C., Giunta, E. F., Signori, A., Rebuzzi, S. E., Banna, G. L., Maniam, A., Buti, S., Cattrini, C., Fornarini, G., Bauckneht, M., Greystoke, A., Plummer, R., Oing, C., & Rescigno, P.
Affiliations
  • Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IT)
  • University of Genoa (IT)
  • Ospedale San Paolo (IT)
  • National Health Service (GB)
  • University of Parma (IT)
  • Azienda Ospedaliero Universitaria Maggiore della Carita (IT)
  • Ospedale Policlinico San Martino (IT)
  • Newcastle University (GB)
  • Universität Hamburg (DE)
  • Candiolo Cancer Institute (IT)
Corresponding author
Rescigno, Pasquale
ORCID
Venue
European Urology Oncology
Publisher
Elsevier BV
Published
2024-04
Volume
7
Issue
2
Pages
179-188
ISSN
2588-9311 (ISSN-L)
DOI
10.1016/j.euo.2023.07.013
OpenAlex
W4385782092
Cited by
39
References
32
Citations by year
2026: 5 · 2025: 22 · 2024: 8
FWCI
1.81
Type
journal article
Language
en
Open access
Licence
Locations
  • European Urology Oncology (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • CINECA IRIS Institutial Research Information System (University of Genoa) (submittedVersion, other-oa)
  • Newcastle University ePrints (Newcastle Univesity) (cc-by-nc-nd)
Funders
  • Prostate Cancer Foundation
  • Ministero della Salute
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Prostate Cancer Treatment and Research
  • Health Sciences › Medicine › Oncology › PARP inhibition in cancer therapy
  • Health Sciences › Medicine › Oncology › Advanced Breast Cancer Therapies
Keywords
PARP inhibitors, metastatic castration-resistant prostate cancer, first-line therapy, combination therapy, homologous recombination deficiency, progression-free survival, overall survival, PROPEL, magnitude
MeSH terms
Poly(ADP-ribose) Polymerase Inhibitors, Progression-Free Survival, Androgen Antagonists, Humans, Male, Receptors, Androgen, Prostatic Neoplasms, Castration-Resistant

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