Evidence map›Paper›PMID 27765535›Full record

SynthesisJournal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer2017

Checkpoint Inhibitors in Metastatic EGFR-Mutated Non-Small Cell Lung Cancer-A Meta-Analysis.

Chee Khoon Lee, Johnathan Man, Sally Lord, Matthew Links, Val Gebski, Tony Mok, James Chih-Hsin Yang

Registry-linked trialOpen access · bronzeAbstract readMeta-Analysis
PubMed Publisher
In one paragraph

Synthesis in Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04141644 (A Phase Ib Study to Evaluate the Safety and Efficacy of Osimertinib in Combination With Ipilimumab in Patients With EGFR Mutated Non-Small-Cell Lung Cancer Tumors), which is not on this map. Cited by 516 papers, 7 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
516citing papers in PubMed, 7 pooled it
74.1field-weighted citation impact, top 1% 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.

NCT04141644 phase1active not recruitingnot on this mapstarted 2020, after this paper: background citation

A Phase Ib Study to Evaluate the Safety and Efficacy of Osimertinib in Combination With Ipilimumab in Patients With EGFR Mutated Non-Small-Cell Lung Cancer Tumors

TypeinterventionalSponsorUniversity of UtahRan2020 to 2028Enrolled24ConditionsNon-Small Cell Lung Cancer With Mutation in Epidermal Growth Factor Receptor (Disorder)ArmsIpilimumab, Osimertinib
3 · Its place in the literature

Who cites it

516 citing papers in PubMed, 7 syntheses or guidelines pooled it, 824 citations in OpenAlex.

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  9. Phase III KEYNOTE-789 Study of Pemetrexed and Platinum With or Without Pembrolizumab for Tyrosine Kinase Inhibitor‒Resistant,Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2024
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  13. Phase III, Randomized Study of Atezolizumab Plus Bevacizumab and Chemotherapy in Patients WithJournal of clinical oncology : official journal of the American Society of Clinical Oncology · 2024
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  17. Tislelizumab plus chemotherapy for patients withJournal for immunotherapy of cancer · 2023
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456 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

7 authors at 4 institutions in 3 countries.

Chee Khoon LeeNational Health and Medical Research Council Clinical Trials Centre, The University of Sydney, Sydney, Australia; Cancer Care Centre, St. George Hospital, Sydney, Australia. Electronic address: chee.lee@ctc.usyd.edu.au.
Johnathan ManCancer Care Centre, St. George Hospital, Sydney, Australia.
Sally LordNational Health and Medical Research Council Clinical Trials Centre, The University of Sydney, Sydney, Australia; School of Medicine, The University of Norte Dame, Sydney, Australia.
Matthew LinksCancer Care Centre, St. George Hospital, Sydney, Australia.
Val GebskiNational Health and Medical Research Council Clinical Trials Centre, The University of Sydney, Sydney, Australia.
Tony MokHong Kong Cancer Institute, Department of Clinical Oncology, Chinese University of Hong Kong, Shatin, People's Republic of China.
James Chih-Hsin YangGraduate Institute of Oncology, National Taiwan University and Department of Oncology, National Taiwan University Hospital, Taipei City, Republic of China.
The University of Sydney · AUSt George Hospital · AUChinese University of Hong Kong · HKNational Taiwan University Hospital · TW

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

introductionWe performed a meta-analysis to assess the role of immune checkpoint inhibitors as second-line therapy in EGFR-mutant advanced NSCLC.

methodsRandomized trials comparing immune checkpoint inhibitors against chemotherapy were identified. We retrieved the hazard ratio (HR) and 95% confidence interval (CI) for overall survival (OS) of the intention-to-treat population and EGFR mutation-defined subgroups. We used the fixed-effects inverse variance-weighted method to pool estimates of treatment efficacy. Statistical tests were two sided.

resultsIn the three included studies that compared immune checkpoint inhibitors (nivolumab [n = 292], pembrolizumab [n = 691], and atezolizumab [n =144]) against docetaxel (n = 776), immune checkpoint inhibitors significantly prolonged OS over that with docetaxel overall (n = 1903, HR = 0.68, 95% CI: 0.61-0.77, p < 0.0001) and in the EGFR wild-type subgroup (n = 1362, HR = 0.66, 95% CI: 0.58-0.76, p < 0.0001) but not in the EGFR-mutant subgroup (n = 186, HR = 1.05, 95% CI: 0.70-1.55, p < 0.81; treatment-mutation interaction p = 0.03).

conclusionIn EGFR-mutant advanced NSCLC, immune checkpoint inhibitors do not improve OS over that with docetaxel. Mechanisms of acquired resistance to first-line tyrosine kinase inhibitor therapy should be elucidated to guide selection of second-line treatment for these patients.

Indexed as

MutationAntineoplastic AgentsCarcinoma, Non-Small-Cell LungCell Cycle CheckpointsErbB ReceptorsHumansImmunotherapyLung NeoplasmsPrognosisRandomized Controlled Trials as TopicAntineoplastic AgentsEGFR protein, humanErbB ReceptorsEGFR mutationImmune checkpoint inhibitorsNSCLCPredictive biomarker

Identifiers

PMID27765535
OpenAlexW2538232731

What OpenQuestion holds

Textmetadata
Read underepoch 390

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.