Efficacy of EGFR Tyrosine Kinase Inhibitors in the Adjuvant Treatment for Operable Non-small Cell Lung Cancer by a Meta-Analysis

Qingyuan Huang; Jinhui Li; Yihua Sun; Rui Wang; Xinghua Cheng; Haiquan Chen

doi:10.1016/j.chest.2015.12.017

Efficacy of EGFR Tyrosine Kinase Inhibitors in the Adjuvant Treatment for Operable Non-small Cell Lung Cancer by a Meta-Analysis

Chest. 2016 Jun;149(6):1384-92. doi: 10.1016/j.chest.2015.12.017. Epub 2015 Dec 24.

Authors

Qingyuan Huang¹, Jinhui Li², Yihua Sun³, Rui Wang¹, Xinghua Cheng¹, Haiquan Chen⁴

Affiliations

¹ Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China.
² School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
³ Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.
⁴ Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China; Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China. Electronic address: hqchen1@yahoo.com.

PMID: 26836897
DOI: 10.1016/j.chest.2015.12.017

Abstract

Background: The role of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in the adjuvant treatment of non-small cell lung cancer (NSCLC) has not been well-established. Our meta-analysis aimed to determine whether the administration of EGFR-TKIs could improve the outcomes of patients with NSCLC undergoing complete resection.

Methods: We comprehensively searched databases and extracted data from eligible studies. Disease-free survival (DFS) and overall survival (OS) with hazard ratios (HRs) as well as disease relapse with odds ratios (OR) were calculated using random and/or fixed-effects models. Meta-regression analysis and test for interaction between subgroups were also carried out.

Results: A total of 1,960 patients in five studies were included. Adjuvant EGFR-TKI treatment was associated with a significant benefit on DFS (HR, 0.63; 95% CI, 0.41-0.99), corresponding to an absolute benefit of 3.1% at 3 years, yet with significant heterogeneity (I(2) = 83.4%, P < .001). The survival benefit was superior (Pinteraction = .03) in studies with more than an 18-month median treatment duration. EGFR mutation rate was also identified as a source of heterogeneity (P = .017). In the population with EGFR mutations, HR for DFS was 0.48 (95% CI, 0.36-0.65), corresponding to an absolute benefit of 9.5% at 3 years, with a reduced risk of distant metastasis (OR, 0.71; 95% CI, 0.56-0.92). Adjuvant EGFR-TKI treatment resulted in a marginally statistically significant benefit on OS (HR, 0.72; 95% CI, 0.49-1.06). The rate of overall grade 3 or greater adverse events was 42.3% (95% CI, 39.1-45.6).

Conclusions: Adjuvant EGFR-TKI treatment may enhance disease-free survival and reduce the risk of distant metastasis in patients with EGFR-mutant NSCLC undergoing complete resection.

Keywords: adjuvant treatment; epidermal growth factor receptor tyrosine kinase inhibitors; non-small cell lung cancer; operable; survival.

Publication types

Meta-Analysis

MeSH terms

Antineoplastic Agents / pharmacology*
Carcinoma, Non-Small-Cell Lung / drug therapy*
Carcinoma, Non-Small-Cell Lung / metabolism
Carcinoma, Non-Small-Cell Lung / pathology
ErbB Receptors / antagonists & inhibitors*
Humans
Lung Neoplasms / drug therapy*
Lung Neoplasms / metabolism
Lung Neoplasms / pathology
Protein Kinase Inhibitors / pharmacology*
Survival Analysis
Treatment Outcome

Substances

Antineoplastic Agents
Protein Kinase Inhibitors
ErbB Receptors