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

doi:10.1001/jama.2014.3314

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

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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Retraction Note to: The Efficacy of Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors for Molecularly Selected Patients with Non-Small Cell Lung Cancer: A Meta-Analysis of 30 Randomized Controlled Trials
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RETRACTED ARTICLE: The Efficacy of Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors for Molecularly Selected Patients with Non-Small Cell Lung Cancer: A Meta-Analysis of 30 Randomized Controlled Trials
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Retracted

The Efficacy of Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors in Non–Small Cell Lung Cancer Harboring Wild-type Epidermal Growth Factor Receptor
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EGFR tyrosine kinase inhibitorsversuschemotherapy inEGFRwild-type pre-treated advanced nonsmall cell lung cancer in daily practice
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[Effectiveness of EGFR-TKIs versus chemotherapy as first-line treatment for advanced non-small cell lung cancer: a meta-analysis].
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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: Hahn, Seokyung
Kim, Dong-Wan
Suh, Koung Jin
Keam, Bhumsuk
Kim, Tae Min
Lee, Se-Hoon
Heo, Dae Seog
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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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

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