Evidence map›Paper›PMID 25657199›Full record

SynthesisThe oncologist2015

The role of smoking status on the progression-free survival of non-small cell lung cancer patients harboring activating epidermal growth factor receptor (EGFR) mutations receiving first-line EGFR tyrosine kinase inhibitor versus platinum doublet chemotherapy: a meta-analysis of prospective randomized trials.

Yoshikazu Hasegawa, Masahiko Ando, Makoto Maemondo, Satomi Yamamoto, Shun-Ichi Isa, Hideo Saka, Akihito Kubo, Tomoya Kawaguchi, Minoru Takada, Rafael Rosell and 2 more

Open access · bronzeAbstract readMeta-Analysis
In one paragraph

Synthesis in The oncologist, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
36citing papers in PubMed, 3 pooled it
6.0field-weighted citation impact, top 3% 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

36 citing papers in PubMed, 3 syntheses or guidelines pooled it, 56 citations in OpenAlex.

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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

12 authors at 11 institutions in 3 countries.

Yoshikazu HasegawaIzumi Municipal Hospital, Osaka, Japan; Nagoya University Hospital, Nagoya, Aichi, Japan; Miyagi Cancer Center, Miyagi, Japan; University of Kansas Cancer Center, Kansas City, Kansas, USA; National Hospital Organization Kinki-Chuo Chest Medical Center, Osaka, Japan; National Hospital Organization Nagoya Medical Center, Aichi, Japan; Aichi Medical University School of Medicine, Nagoya, Aichi, Japan; Graduate School of Medicine, Osaka City University, Osaka, Japan; Koyo Hospital, Wakayama, Japan; Catalan Institute of Oncology, Barcelona, Spain; Kansai Medical University Hirakata Hospital, Osaka, Japan; Chao Family Comprehensive Cancer Center, University of California Irvine School of Medicine, Orange, California, USA.
Masahiko AndoIzumi Municipal Hospital, Osaka, Japan; Nagoya University Hospital, Nagoya, Aichi, Japan; Miyagi Cancer Center, Miyagi, Japan; University of Kansas Cancer Center, Kansas City, Kansas, USA; National Hospital Organization Kinki-Chuo Chest Medical Center, Osaka, Japan; National Hospital Organization Nagoya Medical Center, Aichi, Japan; Aichi Medical University School of Medicine, Nagoya, Aichi, Japan; Graduate School of Medicine, Osaka City University, Osaka, Japan; Koyo Hospital, Wakayama, Japan; Catalan Institute of Oncology, Barcelona, Spain; Kansai Medical University Hirakata Hospital, Osaka, Japan; Chao Family Comprehensive Cancer Center, University of California Irvine School of Medicine, Orange, California, USA Ignatius.ou@uci.edu mando@med.nagoya-u.ac.jp.
Makoto MaemondoIzumi Municipal Hospital, Osaka, Japan; Nagoya University Hospital, Nagoya, Aichi, Japan; Miyagi Cancer Center, Miyagi, Japan; University of Kansas Cancer Center, Kansas City, Kansas, USA; National Hospital Organization Kinki-Chuo Chest Medical Center, Osaka, Japan; National Hospital Organization Nagoya Medical Center, Aichi, Japan; Aichi Medical University School of Medicine, Nagoya, Aichi, Japan; Graduate School of Medicine, Osaka City University, Osaka, Japan; Koyo Hospital, Wakayama, Japan; Catalan Institute of Oncology, Barcelona, Spain; Kansai Medical University Hirakata Hospital, Osaka, Japan; Chao Family Comprehensive Cancer Center, University of California Irvine School of Medicine, Orange, California, USA.
Satomi YamamotoIzumi Municipal Hospital, Osaka, Japan; Nagoya University Hospital, Nagoya, Aichi, Japan; Miyagi Cancer Center, Miyagi, Japan; University of Kansas Cancer Center, Kansas City, Kansas, USA; National Hospital Organization Kinki-Chuo Chest Medical Center, Osaka, Japan; National Hospital Organization Nagoya Medical Center, Aichi, Japan; Aichi Medical University School of Medicine, Nagoya, Aichi, Japan; Graduate School of Medicine, Osaka City University, Osaka, Japan; Koyo Hospital, Wakayama, Japan; Catalan Institute of Oncology, Barcelona, Spain; Kansai Medical University Hirakata Hospital, Osaka, Japan; Chao Family Comprehensive Cancer Center, University of California Irvine School of Medicine, Orange, California, USA.
Shun-Ichi IsaIzumi Municipal Hospital, Osaka, Japan; Nagoya University Hospital, Nagoya, Aichi, Japan; Miyagi Cancer Center, Miyagi, Japan; University of Kansas Cancer Center, Kansas City, Kansas, USA; National Hospital Organization Kinki-Chuo Chest Medical Center, Osaka, Japan; National Hospital Organization Nagoya Medical Center, Aichi, Japan; Aichi Medical University School of Medicine, Nagoya, Aichi, Japan; Graduate School of Medicine, Osaka City University, Osaka, Japan; Koyo Hospital, Wakayama, Japan; Catalan Institute of Oncology, Barcelona, Spain; Kansai Medical University Hirakata Hospital, Osaka, Japan; Chao Family Comprehensive Cancer Center, University of California Irvine School of Medicine, Orange, California, USA.
Hideo SakaIzumi Municipal Hospital, Osaka, Japan; Nagoya University Hospital, Nagoya, Aichi, Japan; Miyagi Cancer Center, Miyagi, Japan; University of Kansas Cancer Center, Kansas City, Kansas, USA; National Hospital Organization Kinki-Chuo Chest Medical Center, Osaka, Japan; National Hospital Organization Nagoya Medical Center, Aichi, Japan; Aichi Medical University School of Medicine, Nagoya, Aichi, Japan; Graduate School of Medicine, Osaka City University, Osaka, Japan; Koyo Hospital, Wakayama, Japan; Catalan Institute of Oncology, Barcelona, Spain; Kansai Medical University Hirakata Hospital, Osaka, Japan; Chao Family Comprehensive Cancer Center, University of California Irvine School of Medicine, Orange, California, USA.
Akihito KuboIzumi Municipal Hospital, Osaka, Japan; Nagoya University Hospital, Nagoya, Aichi, Japan; Miyagi Cancer Center, Miyagi, Japan; University of Kansas Cancer Center, Kansas City, Kansas, USA; National Hospital Organization Kinki-Chuo Chest Medical Center, Osaka, Japan; National Hospital Organization Nagoya Medical Center, Aichi, Japan; Aichi Medical University School of Medicine, Nagoya, Aichi, Japan; Graduate School of Medicine, Osaka City University, Osaka, Japan; Koyo Hospital, Wakayama, Japan; Catalan Institute of Oncology, Barcelona, Spain; Kansai Medical University Hirakata Hospital, Osaka, Japan; Chao Family Comprehensive Cancer Center, University of California Irvine School of Medicine, Orange, California, USA.
Tomoya KawaguchiIzumi Municipal Hospital, Osaka, Japan; Nagoya University Hospital, Nagoya, Aichi, Japan; Miyagi Cancer Center, Miyagi, Japan; University of Kansas Cancer Center, Kansas City, Kansas, USA; National Hospital Organization Kinki-Chuo Chest Medical Center, Osaka, Japan; National Hospital Organization Nagoya Medical Center, Aichi, Japan; Aichi Medical University School of Medicine, Nagoya, Aichi, Japan; Graduate School of Medicine, Osaka City University, Osaka, Japan; Koyo Hospital, Wakayama, Japan; Catalan Institute of Oncology, Barcelona, Spain; Kansai Medical University Hirakata Hospital, Osaka, Japan; Chao Family Comprehensive Cancer Center, University of California Irvine School of Medicine, Orange, California, USA.
Minoru TakadaIzumi Municipal Hospital, Osaka, Japan; Nagoya University Hospital, Nagoya, Aichi, Japan; Miyagi Cancer Center, Miyagi, Japan; University of Kansas Cancer Center, Kansas City, Kansas, USA; National Hospital Organization Kinki-Chuo Chest Medical Center, Osaka, Japan; National Hospital Organization Nagoya Medical Center, Aichi, Japan; Aichi Medical University School of Medicine, Nagoya, Aichi, Japan; Graduate School of Medicine, Osaka City University, Osaka, Japan; Koyo Hospital, Wakayama, Japan; Catalan Institute of Oncology, Barcelona, Spain; Kansai Medical University Hirakata Hospital, Osaka, Japan; Chao Family Comprehensive Cancer Center, University of California Irvine School of Medicine, Orange, California, USA.
Rafael RosellIzumi Municipal Hospital, Osaka, Japan; Nagoya University Hospital, Nagoya, Aichi, Japan; Miyagi Cancer Center, Miyagi, Japan; University of Kansas Cancer Center, Kansas City, Kansas, USA; National Hospital Organization Kinki-Chuo Chest Medical Center, Osaka, Japan; National Hospital Organization Nagoya Medical Center, Aichi, Japan; Aichi Medical University School of Medicine, Nagoya, Aichi, Japan; Graduate School of Medicine, Osaka City University, Osaka, Japan; Koyo Hospital, Wakayama, Japan; Catalan Institute of Oncology, Barcelona, Spain; Kansai Medical University Hirakata Hospital, Osaka, Japan; Chao Family Comprehensive Cancer Center, University of California Irvine School of Medicine, Orange, California, USA.
Takayasu KurataIzumi Municipal Hospital, Osaka, Japan; Nagoya University Hospital, Nagoya, Aichi, Japan; Miyagi Cancer Center, Miyagi, Japan; University of Kansas Cancer Center, Kansas City, Kansas, USA; National Hospital Organization Kinki-Chuo Chest Medical Center, Osaka, Japan; National Hospital Organization Nagoya Medical Center, Aichi, Japan; Aichi Medical University School of Medicine, Nagoya, Aichi, Japan; Graduate School of Medicine, Osaka City University, Osaka, Japan; Koyo Hospital, Wakayama, Japan; Catalan Institute of Oncology, Barcelona, Spain; Kansai Medical University Hirakata Hospital, Osaka, Japan; Chao Family Comprehensive Cancer Center, University of California Irvine School of Medicine, Orange, California, USA.
Sai-Hong Ignatius OuIzumi Municipal Hospital, Osaka, Japan; Nagoya University Hospital, Nagoya, Aichi, Japan; Miyagi Cancer Center, Miyagi, Japan; University of Kansas Cancer Center, Kansas City, Kansas, USA; National Hospital Organization Kinki-Chuo Chest Medical Center, Osaka, Japan; National Hospital Organization Nagoya Medical Center, Aichi, Japan; Aichi Medical University School of Medicine, Nagoya, Aichi, Japan; Graduate School of Medicine, Osaka City University, Osaka, Japan; Koyo Hospital, Wakayama, Japan; Catalan Institute of Oncology, Barcelona, Spain; Kansai Medical University Hirakata Hospital, Osaka, Japan; Chao Family Comprehensive Cancer Center, University of California Irvine School of Medicine, Orange, California, USA Ignatius.ou@uci.edu mando@med.nagoya-u.ac.jp.
Aichi Medical University · JPInstitut Català d'Ornitologia · ESIzumi City General Hospital · JPKansai Medical University · JPMiyagi Prefectural Hospital Organization · JPNagoya Medical Center · JPNagoya University Hospital · JPNational Kinki Chuo Hospital for Chest Disease · JPOsaka City University · JPThe University of Kansas Cancer Center · USUniversity of California, Irvine · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundUnivariate analyses from several randomized phase III trials seemed to suggest ever-smokers with advanced mutated epidermal growth factor receptor (EGFRm) non-small cell lung cancer (NSCLC) did not seem to benefit from EGFR tyrosine kinase inhibitors (TKIs) as first-line treatment when compared with platinum-doublet chemotherapy as measured by progression-free survival (PFS).

methodsA literature-based meta-analysis of PFS outcomes as measured by log-transformed pooled hazard ratio (HR) was performed using a random-effect model. Pooled HRs for smoking status, age, gender, ethnicity, type of EGFR mutation, and EGFR TKI were obtained. Comparison of the pooled HR was performed by metaregression analysis.

resultsAmong the 1,649 EGFRm NSCLC patients analyzed from 7 prospective randomized trials (WJTOG3405, NEJ002, EURTAC, OPTIMAL, LUX Lung-3, LUX Lung-6, and ENSURE), 83.7% were Asians, and 30.0% were ever-smokers. An equal percentage of ever-smokers received doublet chemotherapy (30.2%) or EGFR TKI (30.0%). The pooled HR for PFS was 0.29 (95% confidence interval [CI]: 0.21-0.39) for never-smokers and 0.54 (95% CI: 0.38-0.76) for ever-smokers (p < .007 by metaregression). The pooled PFS HR for exon 19 deletion was 0.25 (95% CI: 0.19-0.31) and 0.44 for exon 21 substitution (95% CI: 0.34-0.57) (p < .001 by metaregression analysis). The pooled PFS HR was 0.33 (95% CI: 0.24-0.46) for Asians and 0.48 for non-Asians (95% CI: 0.28-0.84) (p = .261 by metaregression analysis).

conclusionEGFRm NSCLC patients derived significant PFS benefit from TKI over platinum-doublet chemotherapy as first-line treatment regardless of smoking status; however, PFS benefit is significantly better in never-smokers by metaregression analysis.

Indexed as

Antineoplastic AgentsCarboplatinCarcinoma, Non-Small-Cell LungCisplatinDisease ProgressionErbB ReceptorsHumansLung NeoplasmsMutationPrognosisProspective StudiesProtein Kinase InhibitorsRandomized Controlled Trials as TopicSmokingSurvival RateAntineoplastic AgentsCarboplatinCisplatinErbB ReceptorsProtein Kinase InhibitorsAfatinibEGFR mutant non-small cell lung cancerEGFR TKIsErlotinibGefitinibMeta-analysisSmoking status

Identifiers

PMID25657199
PMCPMC4350797
OpenAlexW2112339468

What OpenQuestion holds

Textmetadata
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.