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Cited by 142Lung Cancer Treatments and MutationsLung Cancer Diagnosis and TreatmentHER2/EGFR in Cancer Research

The DOI matches its Crossref record; 47 of the 47 references it cites were found in a registry or an index.

Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors vs Conventional Chemotherapy in Non–Small Cell Lung Cancer Harboring Wild-Type Epidermal Growth Factor Receptor: A Meta-analysis

Lee, June-Koo, Hahn, Seokyung, Kim, Dong-Wan, Suh, Koung Jin, Keam, Bhumsuk, Kim, Tae Min, Lee, Se-Hoon, Heo, Dae Seog·2014·JAMA
DOI 10.1001/jama.2014.3314
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Abstract

IMPORTANCE: Current guidelines recommend both epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) and cytotoxic chemotherapy drugs as standard treatment options for patients with wild-type (WT) EGFR who were previously treated for non-small cell lung cancer (NSCLC). However, it is not clear that EGFR TKIs are as efficacious as chemotherapy in patients with WT EGFR. OBJECTIVE: To determine the association between first-generation EGFR TKI vs chemotherapy and survival in advanced NSCLC patients with WT EGFR. DATA SOURCES: PubMed, EMBASE, Cochrane database, and meeting abstracts of the American Society of Clinical Oncology and European Society of Medical Oncology through December 2013. STUDY SELECTION: Eligible studies were randomized controlled trials comparing EGFR TKI with conventional chemotherapy in patients with advanced NSCLC. Out of 1947 retrieved articles, 11 trials incorporating 1605 patients with WT EGFR were included. DATA EXTRACTION AND SYNTHESIS: Two reviewers extracted trial characteristics and outcomes. The risk of bias was evaluated using the Cochrane tool. All measures were pooled using random-effects models and 95% CIs were calculated. MAIN OUTCOMES AND MEASURES: The primary outcome was progression-free survival (PFS), measured as hazard ratios (HRs). The secondary outcomes were objective response rate and overall survival, expressed as relative risks and HRs, respectively. RESULTS: Among patients with WT EGFR tumors, chemotherapy was associated with improvement of PFS, compared with TKI (HR for TKI, 1.41; 95% CI, 1.10-1.81). No statistically significant subgroup difference was identified in terms of line of treatment (first-line vs second- or later-line), experimental drug, dominant ethnicity, or EGFR mutation analysis method. Trials using more sensitive platforms than direct sequencing were associated with a significant PFS benefit with chemotherapy (HR for TKI, 1.84; 95% CI, 1.35-2.52). The association of chemotherapy with improvement in PFS was also significant in second- or later-line trials (HR, 1.34; 95% CI, 1.09-1.65). The objective response rate was higher with chemotherapy (92/549, 16.8%, vs 39/540, 7.2%, for TKI; relative risk for TKI, 1.11; 95% CI, 1.02-1.21); however, no statistically significant difference was observed with respect to overall survival (HR for TKI, 1.08; 95% CI, 0.96-1.22). CONCLUSIONS AND RELEVANCE: Among patients with advanced NSCLC harboring WT EGFR, conventional chemotherapy, compared with first-generation EGFR TKI, was associated with improvement in PFS but not overall survival.

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Metadata

Authors
Lee, J.-K., Hahn, S., Kim, D.-W., Suh, K. J., Keam, B., Kim, T. M., Lee, S.-H., & Heo, D. S.
Affiliations
  • Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea
  • Seoul National University (KR)
ORCID
Venue
JAMA
Publisher
American Medical Association (AMA)
Published
2014-04-09
Volume
311
Issue
14
Pages
1430
ISSN
  • 0002-9955 (ISSN-L)
  • 0098-7484
DOI
10.1001/jama.2014.3314
OpenAlex
W2158043872
Cited by
141
References
47
Citations by year
2025: 5 · 2024: 3 · 2023: 6 · 2022: 6 · 2021: 8 · 2020: 7 · 2019: 10 · 2018: 8 · 2017: 24 · 2016: 27 · 2015: 25 · 2014: 12
FWCI
23.55
Type
journal article
Language
en
Open access
closed
Locations
  • JAMA (publishedVersion)
  • PubMed (publishedVersion)
  • Seoul National University Open Repository (Seoul National University) (submittedVersion)
Topics
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Diagnosis and Treatment
  • Health Sciences › Medicine › Oncology › HER2/EGFR in Cancer Research
Keywords
EGFR tyrosine kinase inhibitors, non-small cell lung cancer, EGFR wild-type, cytotoxic chemotherapy, progression-free survival, overall survival, objective response rate, EGFR mutation testing, EGFR mutation status, first-line therapy, second-line therapy, randomized controlled trials meta-analysis, risk of bias assessment, subgroup analysis
MeSH terms
Antineoplastic Agents, Carcinoma, Non-Small-Cell Lung, Humans, Lung Neoplasms, Mutation, Protein-Tyrosine Kinases, Randomized Controlled Trials as Topic, Disease-Free Survival, Protein Kinase Inhibitors, ErbB Receptors

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