358P Adjuvant tyrosine kinase inhibitors in non-squamous non-small cell lung cancer with EGFR driver mutations: An updated meta-analysis of randomized trials

Abstract

Current treatment guidelines state that resectable early stage NSCLC may be treated with adjuvant therapy in the form of chemotherapy and radiotherapy. For Nonsquamous Non-Small Cell Lung Cancer (NS NSCLC), Epidermal Growth Factor Receptor (EGFR) mutations may be present in up to 60% of cases. In the locally advanced and metastatic settings, EGFR tyrosine kinase inhibitors (TKI) have shown remarkable efficacy. With the basis of EGFR as a driver mutation for carcinogenesis, EGFR TKI treatment has been explored in several studies. However, the role of EGFR TKI in the adjuvant setting remains controversial due to lack of conclusive evidence. The latest treatment guidelines do not favor adjuvant EGFR TKI for EGFR-mutant resected early stage NS-NSCLC. Therefore, this meta-analysis evaluated existing randomized controlled trials (RCTs) for a more precise estimate of the efficacy of adjuvant EGFR TKI and associated lung cancer survival. A systematic search of Pubmed, Embase, Cochrane, and clinical trials databases as well as hand search were utilized to identify RCTs investigating adjuvant EGFR TKI treatment in resected NS-NSCLC. Seven RCTs were included (N=2095), all contain disease free survival (DFS) data. Four trials gave EGFR TKI treatment for 24 months, while one trial provided EGFR TKI treatment for 36 months. Erlotinib, gefitinib, icotinib, and osimertinib were the EGFR TKI used in the RCTs. Treatment with adjuvant EGFR TKI showed statistically significant DFS benefit (HR 0.64, 95% CI[0.50-0.82)], P=0.0005) although with substantial heterogeneity (I2=98%, P<0.00001). This heterogeneity was attributed to trial phase and EGFR TKI generation used. Subgroup analyses were done for trial phase, treatment duration, disease stage, type of EGFR TKI, and toxicity. It was found that use of EGFR TKI gefinitib has statistically significant survival (DFS) advantage (HR 0.56, 95% CI(0.47-0.66), P<0.00001; I2=0%). Results of this meta-analysis provide preliminary but strong evidence recommending EGFR TKI in the adjuvant setting among EGFR-mutant resected early NS NSCLC by improving DFS.