Evidence map›Paper›PMID 31023244›Full record

SynthesisBMC cancer2019

Comparative survival benefit of currently licensed second or third line treatments for epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) negative advanced or metastatic non-small cell lung cancer: a systematic review and secondary analysis of trials.

Martin Connock, Xavier Armoiry, Alexander Tsertsvadze, G J Melendez-Torres, Pamela Royle, Lazaros Andronis, Aileen Clarke

Open access · goldAbstract readNetwork Meta-AnalysisSystematic Review
In one paragraph

Synthesis in BMC cancer, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed, 2 pooled it
1.0field-weighted citation impact, top 21% 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

3 citing papers in PubMed, 2 syntheses or guidelines pooled it, 10 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. 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

7 authors at 4 institutions in 3 countries.

Martin ConnockWarwick Medical School, Division of Health Sciences, University of Warwick, Gibbet Hill road, CV47AL, Coventry, England.
Xavier ArmoiryWarwick Medical School, Division of Health Sciences, University of Warwick, Gibbet Hill road, CV47AL, Coventry, England. armoiryxa@gmail.com.ORCID http://orcid.org/0000-0003-1166-0453
Alexander TsertsvadzeWarwick Medical School, Division of Health Sciences, University of Warwick, Gibbet Hill road, CV47AL, Coventry, England.
G J Melendez-TorresPeninsula Technology AssessmentGroup (PenTAG), University of Exeter, Exeter, UK.
Pamela RoyleWarwick Medical School, Division of Health Sciences, University of Warwick, Gibbet Hill road, CV47AL, Coventry, England.
Lazaros AndronisWarwick Medical School, Division of Health Sciences, University of Warwick, Gibbet Hill road, CV47AL, Coventry, England.
Aileen ClarkeWarwick Medical School, Division of Health Sciences, University of Warwick, Gibbet Hill road, CV47AL, Coventry, England.
University of Warwick · GBUniversité Claude Bernard Lyon 1 · FRUniversity of Exeter · GBUniversity of Ottawa · CA

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundA review of therapies for advanced cancers licenced by the EMA between 2009 and 2013 concluded that for more than half of these drugs there was little evidence of overall survival or quality of life benefit. Recent years have witnessed a growing number of licensed second-line pharmacotherapies for advanced/metastatic non-small cell lung cancer (NSCLC). With the aim of gauging patient survival benefit, we conducted a systematic review of randomised controlled trials (RCT) and compared survival outcomes from available licensed treatments for patients with advanced/metastatic NSCLC.

methodsRCTs of second/third line treatments in participants with advanced/metastatic NSCLC and negative/low expression of Anaplastic Lymphoma Kinase (ALK) and of Epidermal Growth Factor Receptor (EGFR) were included. We searched electronic databases (MEDLINE; EMBASE; Web of Science) from January, 2000 up to July, 2017. Two or more independent reviewers screened bibliographic records, extracted data, and assessed risk of bias of studies. Published Kaplan Meier plots for OS and PFS along with restricted-mean-survival methods and parametric modelling were used to estimate the survival outcomes as mean number of months of survival. Network meta-analysis was undertaken to rank interventions and to make indirect comparisons.

resultsWe included 11 RCTs with data for 7581 participants that compared nine different drugs. In studies of patients regardless of histology groups, targeted drugs (ramucirumab and nintedanib) yielded small overall survival gains of < 2.5 months over docetaxel, erlotinib provided no benefit, while immunotherapies (atezolizumab and pembrolizumab) delivered 5 to 6 months gain. Studies with patients stratified by histology confirmed the apparent superiority of immunotherapy (nivolumab and atezolizumab) over targeted treatments (ramucirumab, nintedanib, afatinib) providing between about 4 to 8 months OS gain over docetaxel. In network analysis immunotherapies consistently ranked higher than alternatives irrespective of population histology and outcome measure.

conclusionOur review indicates that nivolumab, pembrolizumab and atezolizumab provide superior survival benefits compared to other licensed drugs for late stage NSCLC. Patient gains from these immunotherapies are substantial compared to the expected average survival with chemotherapy (docetaxel) of < 1 year for people with squamous histology and about 1.25 year for those with non-squamous histology.

Indexed as

Anaplastic Lymphoma KinaseAntineoplastic Combined Chemotherapy ProtocolsCarcinoma, Non-Small-Cell LungAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedErbB ReceptorsErlotinib HydrochlorideHumansImmunotherapyNeoplasm MetastasisNeoplasms, Second PrimaryProgression-Free SurvivalProtein Kinase InhibitorsQuality of LifeRamucirumabRandomized Controlled Trials as TopicAnaplastic Lymphoma KinaseAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedatezolizumabEGFR protein, humanErbB ReceptorsErlotinib HydrochlorideProtein Kinase InhibitorsRamucirumabAdvanced NSCLCCheck point inhibitorsImmunotherapiesLicensed drugsTargeted therapies

Identifiers

PMID31023244
PMCPMC6485098
OpenAlexW2945103009

What OpenQuestion holds

Textmetadata
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.