Evidence map›Paper›PMID 38994249›Full record

SynthesisBladder cancer (Amsterdam, Netherlands)2023

PARP Inhibitors for Metastatic Urothelial Carcinoma: A Systematic Review of Efficacy and Safety.

Simon J Crabb, Taha Khalid, Lois Woods, Geoff Frampton, Jonathan Shepherd

Abstract readSystematic Review
In one paragraph

Synthesis in Bladder cancer (Amsterdam, Netherlands), 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–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. Review
  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

5 authors.

Simon J CrabbSchool of Cancer Sciences, Faculty of Medicine, University of Southampton, Southampton, UK.
Taha KhalidDepartment of Medical Oncology, University Hospital Southampton NHS Foundation Trust, Southampton, UK.
Lois WoodsSouthampton Health Technology Assessments Centre, Faculty of Medicine, University of Southampton, Southampton, UK.
Geoff FramptonSouthampton Health Technology Assessments Centre, Faculty of Medicine, University of Southampton, Southampton, UK.
Jonathan ShepherdSouthampton Health Technology Assessments Centre, Faculty of Medicine, University of Southampton, Southampton, UK.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundPoly (ADP-ribose) polymerase (PARP) inhibitors have activity in various cancers. Metastatic urothelial carcinoma (MUC) is platinum sensitive and a subset harbour DNA repair gene alterations.

objectiveTo assess evidence for efficacy and safety of PARP inhibition for MUC.

methodsThis systematic review included randomised clinical trials (RCTs) evaluating PARP inhibitors as monotherapy, or in therapeutic combinations, compared to relevant comparators or best supportive care. The primary endpoint was progression free survival (PFS). We searched MEDLINE (Ovid), EMBASE, ClinicalTrials.gov and Cochrane Central Register of Controlled Trials from March 2013 to March 2023. Each study was appraised using the Cochrane Risk of Bias 2 Tool. Study results were synthesised descriptively. Registration: PROSPERO CRD42023403145.

resultsFrom 247 identified reports, we included three phase 2 RCTs including 252 patients. Two RCTs assessed PARP inhibition in unselected patient groups (one first line platinum ineligible, one post chemotherapy maintenance) and found no evidence of efficacy. All three RCTs assessed subgroups defined by biomarker selection for somatic DNA repair defects. Two of these identified PFS benefit with PARP inhibition compared to a relevant comparator (one first line in combination with immunotherapy, one maintenance monotherapy). Safety outcomes were consistent with prior experience of PARP inhibitors. The risk of bias across the outcomes was generally low.

conclusionsPARP inhibitors lack efficacy for unselected MUC patients. Phase 2 RCTs support further investigation of PARP inhibition within biomarker-selected patient subsets. The optimal biomarker is not yet determined. Limitations in the current evidence relate to small sample sizes and low statistical power.

Indexed as

biomarkerBladder cancerhomologous recombination deficiencyimmunotherapymaintenance therapyPARP inhibitorsystematic reviewurothelial carcinoma

Identifiers

PMID38994249
PMCPMC11165942

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Registered trials

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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.