Evidence map›Paper›PMID 28945858›Full record

SynthesisAnnals of oncology : official journal of the European Society for Medical Oncology2017

Tumour- and class-specific patterns of immune-related adverse events of immune checkpoint inhibitors: a systematic review.

L Khoja, D Day, T Wei-Wu Chen, L L Siu, A R Hansen

Registry-linked trialAbstract readSystematic Review
PubMed Publisher
In one paragraph

Synthesis in Annals of oncology : official journal of the European Society for Medical Oncology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03673332 (Elderly Cancer PatIents Treated for Advanced or Metastatic Melanoma or NSCLC, Safety and qualiTy of Life Under immunOtheraPies), which is not on this map. Cited by 545 papers, 18 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
545citing papers in PubMed, 18 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.

NCT03673332 phase4terminatednot on this mapstarted 2019, after this paper: background citation

Elderly Cancer PatIents Treated for Advanced or Metastatic Melanoma or NSCLC, Safety and qualiTy of Life Under immunOtheraPies: a Phase IV Trial

TypeinterventionalSponsorInstitut Paoli-CalmettesRan2019 to 2024Enrolled40ConditionsAdvanced or Metastatic Melanoma, Advanced or Metastatic NSCLCArmsimmune-checkpoint inhibitors therapies
3 · Its place in the literature

Who cites it

545 citing papers in PubMed, 18 syntheses or guidelines pooled it.

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485 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

5 authors.

L KhojaClinical Development Unit, Early Clinical Development, AstraZeneca UK plc, Melbourn Science Park, Melbourn, Hertfordshire;; Medical Oncology, Addenbrookes Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge Biomedical Campus, Cambridge, UK.
D DayDrug Development Program, Division of Medical Oncology and Haematology, Princess Margaret Cancer Centre, Toronto;; Department of Medicine, University of Toronto, Toronto;; Ontario Institute for Cancer Research (OICR), Toronto, Canada.
T Wei-Wu ChenDepartment of Oncology, National Taiwan University Hospital, Taipei;; National Taiwan University Cancer Center, Taipei;; Graduate Institute of Oncology, National Taiwan University College of Medicine, Taipei, Taiwan.
L L SiuDrug Development Program, Division of Medical Oncology and Haematology, Princess Margaret Cancer Centre, Toronto;; Department of Medicine, University of Toronto, Toronto.
A R HansenDrug Development Program, Division of Medical Oncology and Haematology, Princess Margaret Cancer Centre, Toronto;; Department of Medicine, University of Toronto, Toronto;. Electronic address: Aaron.Hansen@uhn.ca.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundImmune checkpoint inhibitor (ICI) monoclonal antibodies (mAbs) targeting cytotoxic T-lymphocyte antigen 4 (CTLA-4), programmed cell death protein 1 (PD-1) or its ligand (PD-L1) produce unique toxicity profiles. The objective of this review was to identify patterns and incidence of immune-related adverse events (irAE) based on tumour type and ICI class.

methodsMedline, EMBASE and COCHRANE databases were searched to identify prospective monotherapy trials of ICIs from 2003 to November 2015. Paired reviewers selected studies for inclusion and extracted data. Odds ratio (OR), χ2 tests and multivariable regression models were used to analyse for effect size and associations.

resultsWe identified 48 trials (6938 patients), including 26 CTLA-4, 17 PD-1, 2 PD-L1 trials, and 3 studies tested both CTLA-4 and PD-1. Grade 3/4 irAE were more common with CTLA-4 mAbs compared with PD-1 (31% versus 10%). All grades colitis (OR 8.7, 95% CI 5.8-12.9), hypophysitis (OR 6.5, 95% CI 3.0-14.3) and rash (OR 2.0, 95% CI 1.8-2.3) were more frequent with CTLA-4 mAbs; whereas pneumonitis (OR 6.4, 95% CI 3.2-12.7), hypothyroidism (OR 4.3, 95% CI 2.9-6.3), arthralgia (OR 3.5, 95% CI 2.6-4.8) and vitiligo (OR 3.5, 95% CI 2.3-5.3) were more common with PD-1 mAbs. Comparison of irAE from the three most studied tumour types in PD-1 mAbs trials [melanoma (n = 2048), non-small-cell lung cancer (n = 1030) and renal cell carcinoma (n = 573)] showed melanoma patients had a higher frequency of gastrointestinal and skin irAE and lower frequency of pneumonitis. DISCUSSION: CTLA-4 and PD-1 mAbs have distinct irAE profiles. Different immune microenvironments may drive histology-specific irAE patterns. Other tumour-dependent irAE profiles may be identified as data emerge from ICI trials.

Indexed as

Antibodies, MonoclonalAntineoplastic Agents, ImmunologicalClinical Trials as TopicCTLA-4 AntigenHumansImmune System DiseasesNeoplasmsProgrammed Cell Death 1 ReceptorRandomized Controlled Trials as TopicAntibodies, MonoclonalAntineoplastic Agents, ImmunologicalCTLA-4 AntigenCTLA4 protein, humanPDCD1 protein, humanProgrammed Cell Death 1 Receptorimmune checkpoint inhibitorsimmune-related adverse events

Identifiers

PMID28945858

What OpenQuestion holds

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Registered trials

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.