Evidence map›Paper›PMID 40246801›Full record

SynthesisTargeted oncology2025

The Impact of Uncommon HRR Alterations as Predictors of Efficacy of PARP Inhibitors in Metastatic Castration-Resistant Prostate Cancer: A Meta-Analysis of Randomized Controlled Trials.

Giada Pinterpe, Fortuna Migliaccio, Chiara Ciccarese, Romina Rose Pedone, Rachele Belletto, Pierluigi Russo, Angelo Totaro, Luca Tagliaferri, Chiara Sighinolfi, Luigi Formisano and 4 more

Abstract readMeta-AnalysisSystematic Review
PubMed Publisher
In one paragraph

Synthesis in Targeted oncology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed, 1 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

2 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Article
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

14 authors.

Giada PinterpeClinica Oncologica e Centro Regionale di Genetica Oncologica, AOU delle Marche, Ancona, Italy.
Fortuna MigliaccioDepartment of Clinical Medicine and Surgery, University of Naples "Federico II", Napoli, Italy.
Chiara CiccareseMedical Oncology, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Largo Agostino Gemelli 8, 00158, Rome, Italy. chiara.ciccarese@policlinicogemelli.it.ORCID http://orcid.org/0000-0002-3283-4339
Romina Rose PedoneUniversità Cattolica del Sacro Cuore, Facoltà di Medicina e Chirurgia, Rome, Italy.
Rachele BellettoUniversità Cattolica del Sacro Cuore, Facoltà di Medicina e Chirurgia, Rome, Italy.
Pierluigi RussoUrology Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.
Angelo TotaroUrology Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.
Luca TagliaferriDepartment of Radiation Oncology, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy.
Chiara SighinolfiUrology Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.
Luigi FormisanoDepartment of Clinical Medicine and Surgery, University of Naples "Federico II", Napoli, Italy.
Rossana BerardiClinica Oncologica e Centro Regionale di Genetica Oncologica, AOU delle Marche, Ancona, Italy.
Bernardo RoccoUrology Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.
Giampaolo TortoraMedical Oncology, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Largo Agostino Gemelli 8, 00158, Rome, Italy.
Roberto IacovelliMedical Oncology, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Largo Agostino Gemelli 8, 00158, Rome, Italy.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundMetastatic castration-resistant prostate cancer (mCRPC) patients with BRCA1/2 mutations show significant responses to poly-ADP ribose polymerase inhibitors (PARPi), while the efficacy of these agents in patients with homologous recombination repair (HRR) gene alterations other than BRCA remains unclear.

objectiveThis meta-analysis aimed at assessing the efficacy of PARPi in mCRPC harboring alterations in four rare HRR genes (i.e. CDK12, PALB2, ATM, and CHEK2). PATIENTS AND

methodsFive randomised phase III trials (PROfound, PROpel, MAGNITUDE, TALAPRO-2, TRITON3) were selected through searching the Medline/PubMed, Cochrane Library, and ASCO Meeting abstracts. Data extraction followed the PRISMA statement. The primary endpoints, radiographic progression-free survival (rPFS) and overall survival (OS) with the relative 95% CI, were calculated using fixed- or random-effects methods, depending on the studies' heterogeneity. RevMan software for meta-analysis (v.5.2.3) was used.

resultsPARPi significantly improved rPFS in mCRPC patients with CDK12 alterations (hazard ratio (HR) = 0.65; p = 0.02) without OS benefit. In patients with ATM, CHEK2, or PALB2 alterations, no significant benefit was observed in rPFS or OS. Due to the low incidence of these rare mutations, we grouped them into gene panels, revealing a significant rPFS advantage when CDK12+PALB2 (HR = 0.63; p = 0.009) were combined, and a similar benefit when including CHEK2 in the gene panel (HR = 0.69; p = 0.01).

conclusionCDK12 alterations could be considered as a predictive biomarker of rPFS benefit with PARPi. A gene panel grouping CDK12 and PALB2 with or without CHEK2 mutations could also enable prediction of rPFS benefit with PARPi.

Indexed as

Poly(ADP-ribose) Polymerase InhibitorsProstatic Neoplasms, Castration-ResistantRecombinational DNA RepairHumansMaleNeoplasm MetastasisRandomized Controlled Trials as TopicPoly(ADP-ribose) Polymerase Inhibitors

Identifiers

PMID40246801

What OpenQuestion holds

Textmetadata
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 OpenQuestion graph.