Evidence map›Paper›PMID 39848867›Full record

SynthesisEuropean urology2025

Heterogeneity of the Treatment Effect with PARP Inhibitors in Metastatic Castration-resistant Prostate Cancer: A Living Interactive Systematic Review and Meta-analysis.

Syed Arsalan Ahmed Naqvi, Irbaz Bin Riaz, Arifa Bibi, Muhammad Ali Khan, Manal Imran, Kaneez Zahra Rubab Khakwani, Ammad Raina, Muhammad Umair Anjum, Ewan K Cobran, Jeremy L Warner and 11 more

Abstract readMeta-AnalysisSystematic Review
PubMed Full text at PMC Publisher
In one paragraph

Synthesis in European urology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed, 3 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

20 citing papers in PubMed, 3 syntheses or guidelines pooled it.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Trial
  5. Review
  6. Review
  7. Article
  8. Review
  9. Review
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  11. Review
  12. Biomarkers and testing in pathology.Current opinion in urology · 2026
    Review
  13. Article
  14. CDK12 and CDK13 in oncology: from RNA regulation to therapeutic targeting.Cellular oncology (Dordrecht, Netherlands) · 2026
    Review
  15. Article
  16. Article
  17. Review
  18. Article
  19. Article
  20. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

21 authors.

Syed Arsalan Ahmed NaqviDivision of Hematology and Oncology, Department of Medicine, Mayo Clinic, Phoenix, AZ, USA.
Irbaz Bin RiazDivision of Hematology and Oncology, Department of Medicine, Mayo Clinic, Phoenix, AZ, USA. Electronic address: riaz.irbaz@mayo.edu.
Arifa BibiDepartment of Internal Medicine, University of Oklahoma, Oklahoma City, OK, USA.
Muhammad Ali KhanDivision of Hematology and Oncology, Department of Medicine, Mayo Clinic, Phoenix, AZ, USA.
Manal ImranDepartment of Internal Medicine, Dow University of Health Sciences, Karachi, Pakistan.
Kaneez Zahra Rubab KhakwaniDepartment of Internal Medicine, The University of Arizona, Tucson, AZ, USA.
Ammad RainaDepartment of Internal Medicine, Canyon Vista Medical Center, Midwestern University, Sierra Vista, AZ, USA.
Muhammad Umair AnjumDivision of Hematology and Oncology, Department of Medicine, Mayo Clinic, Phoenix, AZ, USA.
Ewan K CobranDivision of Epidemiology, Department of Quantitative Health Sciences, Mayo Clinic, Scottsdale, AZ, USA.
Jeremy L WarnerCenter for Clinical Cancer Informatics and Data Science, Legorreta Cancer Center, Brown University, Providence, RI, USA.
Syed A HussainDepartment of Oncology and Metabolism, University of Sheffield, Sheffield, UK.
Parminder SinghDivision of Hematology and Oncology, Department of Medicine, Mayo Clinic, Phoenix, AZ, USA.
Daniel S ChildsDepartment of Oncology, Mayo Clinic, Rochester, MN, USA.
Sylvan C BacaDepartment of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Jacob J OrmeDepartment of Oncology, Mayo Clinic, Rochester, MN, USA.
Joaquin MateoDepartment of Medical Oncology, Vall d'Hebron Institute of Oncology, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain.
Neeraj AgarwalDivision of Medical Oncology, Department of Internal Medicine, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA.
Silke GillessenDepartment of Oncology, Oncology Institute of Southern Switzerland, Ente Ospedaliero Cantonale, Bellinzona, Switzerland; Università della Svizzera Italiana, Lugano, Switzerland.
Mohammad Hassan MuradEvidence-Based Practice Center, Mayo Clinic, Rochester, MN, USA.
Oliver SartorDepartment of Oncology, Mayo Clinic, Rochester, MN, USA.
Alan H BryceDepartment of Oncology, City of Hope Cancer Center, Goodyear, AZ, USA.

Funding

Enhancing the HemOnc Knowledgebase of Chemotherapy Drugs and RegimensU24CA265879 · NCI · RHODE ISLAND HOSPITAL · 2022 to 2025
$1.4M
NCI NIH HHS K01 CA230193NCI NIH HHS U24 CA265879
6 · The paper itself

Abstract

BACKGROUND AND

objectiveSelection of patients harboring mutations in homologous recombination repair (HRR) genes for treatment with a PARP inhibitor (PARPi) is challenging in metastatic castration-resistant prostate cancer (mCRPC). To gain further insight, we quantitatively assessed the differential efficacy of PARPi therapy among patients with mCRPC and different HRR gene mutations.

methodsThis living meta-analysis (LMA) was conducted using the Living Interactive Evidence synthesis framework. We included clinical trials assessing PARPi as monotherapy in pretreated mCRPC or in combination with an androgen receptor pathway inhibitor (ARPI) in treatment-naïve patients. Random-effects meta-analyses were performed for a priori subgroups stratified by HRR status, BRCA status, and each gene. KEY FINDINGS AND LIMITATIONS: This first report for our LMA includes 13 trials (4278 patients). Among patients with pretreated mCRPC receiving PARPi monotherapy, the tumor response rate per 100 person-months was numerically higher for patients with BRCA2 (50% prostate-specific antigen response [PSA50%] 3.3; objective response rate [ORR] 3.3), BRCA1 (PSA50% 1.2; ORR 2.0), or PALB2 (PSA50% 3.3; ORR 1.4) alterations than for patients with ATM (PSA50% 0.4; ORR 0.3), CDK12 (PSA50% 0.2; ORR 0.2), or CHEK2 (PSA50% 1.0; ORR 0.7) alterations. Among patients receiving PARPi + ARPI, a significant radiographic progression-free survival benefit was observed in those with BRCA (hazard ratio [HR] 0.28, 95% confidence interval [CI] 0.13-0.62) or CDK12 (HR 0.58, 95% CI 0.35-0.95) alterations, but not in patients with PALB2 (HR 0.53, 95% CI 0.21-1.32), ATM (HR 0.93, 95% CI 0.57-1.53), or CHEK2 (HR 0.92, 95% CI 0.53-1.61) alterations. An overall survival benefit was observed for patients with BRCA alterations (HR 0.47, 95% CI 0.31-0.71) after adjustment for crossover and subsequent therapy, but not for patients with PALB2 (HR 0.33, 95% CI 0.10-1.16), ATM (HR 0.97, 95% CI 0.57-1.67), CDK12 (HR 0.80, 95% CI 0.36-1.78), or CHEK2 (HR 0.81, 95% CI 0.37-1.75) alterations. CONCLUSIONS AND CLINICAL IMPLICATIONS: Our LMA delivers information on the effect of PARPi therapy in relation to specific gene alterations in mCRPC via an interactive web platform. The evidence suggests the greatest PARPi benefit in patients with BRCA alterations, a strong signal of benefit in patients with PALB2 or CDK12 alterations, and no benefit in patients with ATM or CHEK2 alterations.

Indexed as

Poly(ADP-ribose) Polymerase InhibitorsProstatic Neoplasms, Castration-ResistantBRCA2 ProteinHumansMaleMutationNeoplasm MetastasisRecombinational DNA RepairTreatment OutcomeBRCA2 ProteinPoly(ADP-ribose) Polymerase InhibitorsAndrogen receptor pathway inhibitorsGene-specific therapyHomologous recombination repairLiving interactive meta-analysisMetastatic castration-resistant prostate cancerPARP inhibitors

Identifiers

PMID39848867
PMCPMC13404184

What Socratic holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.