The role of EGFR-TKIs as adjuvant therapy in EGFR mutation-positive early-stage NSCLC: A meta-analysis

Abstract

Background: The role of adjuvant epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) is not clear in early-stage nonsmall-cell lung cancer (NSCLC) patients. This meta-analysis aims to compare the efficacy and safety of EGFR-TKIs as adjuvant therapy with chemotherapy or placebo in NSCLC patients harboring EGFR mutations.

Patients and methods: Pubmed, Embase, and Cochrane databases were searched for randomized controlled trials. The hazard ratio (HR) of disease-free survival (DFS) and overall survival (OS) as well as the risk ratio (RR) of severe adverse events were merged.

Results: Seven articles from five studies from 1843 records, a total of 1227 patients, were included in the analysis. The HR for DFS was 0.38 (95% confidence interval [CI] 0.22-0.63), in favor of EGFR-TKIs. However, no significant benefit of OS was seen (HR = 0.61, 95% CI 0.31-1.22). Treatment benefit was more pronounced in patients with advanced disease stage and longer duration of medication, EGFR exon 19 deletion mutation, and treatment with third-generation EGFR-TKIs. Adjuvant targeted therapy may cause few adverse events compared with chemotherapy (RR = 0.28, 95% CI 0.09-0.94). The possibility of severe adverse events for the first-generation drugs was significantly lower than for third-generation drugs.

Conclusion: In EGFR mutation-positive patients with stage IB-IIIA NSCLC, compared with adjuvant chemotherapy or placebo, adjuvant EGFR-TKIs should effectively improve the patient's DFS, but not effectively improve OS. Disease stage, treatment duration, mutation types, and therapeutic drugs could affect the degree of benefit. Adjuvant EGFR-TKIs had more favorable tolerability than chemotherapy, especially with the usage of first-generation drugs.

Keywords: adjuvant treatment; epidermal growth factor receptor tyrosine kinase inhibitors; nonsmall-cell lung cancer; survival; targeted therapy.