• Ruifeng Liu, Shihong Wei, Qiuning Zhang, Xueliang Zhang, Hongtao Luo, Jinhui Tian, Yi Li, Long Ge, and Xiaohu Wang.
• The First Clinical Medical College of Lanzhou University.
• Medicine (Baltimore). 2019 Jul 1; 98 (29): e16427e16427.

BackgroundPreclinical in vitro experiments demonstrated that epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) might have synergistic effect in combination with radiotherapy on Non-small cell lung cancer (NSCLC), but the clinical trials showed inconsistence results in NSCLC patients with EGFR status unknow or mutations. This study aimed to determine if added TKIs to Thoracic radiotherapy (TRT) improve primary disease response rate (RR) and survival outcomes in advanced or metastatic NSCLC.MethodsWe searched MEDLINE, EMBASE, and Cochrane Library from January 2000 to December 2017 for eligible studies where patients received concurrent EGFR TKIs and TRT or CRT. Concerned outcomes were primary tumor RR, overall survival (OS), and adverse events (AEs). The meta-analysis was performed using Stata software (version 12.0). Random effects models were used to pool outcomes across studies. Sensitivity analysis was performed to determine if the results would be different.ResultsWe found 16 prospective clinical trials with mature results for meta-analyses. Twelve studies including 446 patients reported the RR and survival outcomes of TRT combined TKIs. The CR, PR, SD, and PD, respectively, were 0.06 (95% CI 0.03-0.09, I = 0%), 0.44 (95% CI 0.38-0.49, I = 64.9%), 0.29 (95% CI 0.24-0.34, I = 78.4%), and 0.15 (95% CI 0.11-0.19, I = 84.2%). One- and 2-year OS, respectively, were 0.52 (95% CI 0.44-0.60, I = 38.8%) and 0.26 (95% CI 0.18-0.33, I = 0%). Four studies including 182 patients reported the RR and survival outcomes of CRT combined TKIs. The pooled CR, PR, SD, and PD, respectively, were 0.12 (95% CI 0.02-0.22, I = 69.1%), 0.41 (95% CI 0.27-0.55, I71.6%), 0.31 (95% CI 0.16-0.46, I = 79%), and 0.14 (95% CI -0.01-0.30, I = 87.8%). Only 1 study reported the survival event rate, 1- and 2-year OS, respectively, were 0.83 (95% CI 0.71-0.94) and 0.67 (95% CI 0.54-0.81). There were not severe adverse events (SAEs) reported either TRT combined TKIs or CRT combined TKIs.ConclusionThere is evidence, albeit of low quality, that added the TKIs to TRT or CRT may improve RR and survival outcomes in patients with EGFR mutant status unknown advanced or metastatic NSCLC relative to other studies of TKIs alone, TRT alone or CRT.

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