Journal
CHEST
Volume 149, Issue 6, Pages 1384-1392Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.chest.2015.12.017
Keywords
adjuvant treatment; epidermal growth factor receptor tyrosine kinase inhibitors; non-small cell lung cancer; operable; survival
Categories
Funding
- National Natural Science Foundation of China [81330056, 81472173, 81401891, 81572253, 81372525]
- Key Project of Science and Technology Commission of Shanghai Municipality [JGGG1302]
- Shanghai Hospital Development Center [SHDC12012308]
- Health and Family Planning Commission of Shanghai Municipality [2013ZYJB0301]
- Science and Technology Commission of Shanghai Municipality [14495810800]
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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 (P-interaction = .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.
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