Evidence map›Paper›PMID 34129290›Full record

Observational studyPharmacology research & perspectives2021

Overall survival in metastatic melanoma correlates with pembrolizumab exposure and T cell exhaustion markers.

Vishal Navani, Moira C Graves, Giovana Celli Marchett, Hiren Mandaliya, Nikola A Bowden, Andre van der Westhuizen

Open access · goldAbstract readObservational Study
In one paragraph

Observational study in Pharmacology research & perspectives, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
0.7field-weighted citation impact, top 27% of its field
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

6 citing papers in PubMed, 9 citations in OpenAlex.

  1. Trial
  2. Review
  3. Review
  4. Article
  5. Review
  6. Observational
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

6 authors at 2 institutions in 1 country.

Vishal NavaniCalvary Mater Hospital Newcastle, Waratah, NSW, Australia.ORCID 0000-0002-6795-009X
Moira C GravesCentre for Drug Repurposing and Medicines Research, University of Newcastle and Hunter Medical Research Institute, Callaghan, NSW, Australia.ORCID 0000-0002-3380-5417
Giovana Celli MarchettCalvary Mater Hospital Newcastle, Waratah, NSW, Australia.
Hiren MandaliyaCalvary Mater Hospital Newcastle, Waratah, NSW, Australia.ORCID 0000-0003-0824-7385
Nikola A BowdenCentre for Drug Repurposing and Medicines Research, University of Newcastle and Hunter Medical Research Institute, Callaghan, NSW, Australia.ORCID 0000-0002-6047-1694
Andre van der WesthuizenCalvary Mater Hospital Newcastle, Waratah, NSW, Australia.
Hunter Medical Research Institute · AUCalvary Mater Newcastle Hospital · AU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Trial data support an absence of an exposure-survival relationship for pembrolizumab. As these relationships remain unexamined in a real-world setting, we determined them in metastatic melanoma prospectively in an observational study. Translational objectives included identifying biomarkers of progressive disease (PD). Checkpoint blockade naïve patients receiving 2 mg/kg Q3W pembrolizumab had pharmacokinetic and clinical outcome data collected. Trough, a valid surrogate for drug exposure, was assessed using ELISA. T-cell exhaustion and chemokine markers were determined using flow cytometry. Geometric means of exposures and biomarkers were tested against objective response groups using one-way ANOVA. The cohort was split by the median into high versus low pembrolizumab exposure groups. Kaplan-Meier progression-free survival (PFS) and overall survival (OS) curves were estimated for high versus low exposure, compared using the log rank test. The high pembrolizumab exposure group (n = 14) experienced substantially longer median OS (not reached vs. 48 months, p = .014), than the low exposure group (n = 14). A similar positive exposure PFS relationship was found (median not reached vs. 48 months, p = .045). The frequency of TIM-3 expression on CD4

Indexed as

AdultAgedAged, 80 and overAntibodies, Monoclonal, HumanizedHepatitis A Virus Cellular Receptor 2HumansImmune Checkpoint InhibitorsKaplan-Meier EstimateMelanomaMiddle AgedProgression-Free SurvivalReceptors, CXCR6T-LymphocytesAntibodies, Monoclonal, HumanizedCXCR6 protein, humanHAVCR2 protein, humanHepatitis A Virus Cellular Receptor 2Immune Checkpoint InhibitorspembrolizumabReceptors, CXCR6CXCR6drug exposureimmune checkpoint blockademetastatic melanomapembrolizumabpharmacokineticsTIM-3

Identifiers

PMID34129290
PMCPMC8204864
OpenAlexW3170304773

What OpenQuestion holds

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LicenceCC BY
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.