Epidermal growth factor receptor tyrosine kinase inhibitors combined with thoracic radiotherapy or chemoradiotherapy for advanced or metastatic non-small cell lung cancer: A systematic review and meta-analysis of single-arm trials

Abstract

Background: Preclinical 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. Methods: We 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. Results: We 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 2 = 0%), 0.44 (95% CI 0.38–0.49, I 2 = 64.9%), 0.29 (95% CI 0.24–0.34, I 2 = 78.4%), and 0.15 (95% CI 0.11–0.19, I 2 = 84.2%). One- and 2-year OS, respectively, were 0.52 (95% CI 0.44–0.60, I 2 = 38.8%) and 0.26 (95% CI 0.18–0.33, I 2 = 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 2 = 69.1%), 0.41 (95% CI 0.27–0.55, I 2 = 71.6%), 0.31 (95% CI 0.16–0.46, I 2 = 79%), and 0.14 (95% CI −0.01–0.30, I 2 = 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. Conclusion: There 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.

hTERT promoter methylation promotes small cell lung cancer progression and radiotherapy resistance

“…Radiation therapy has been widely used since 1992. However, accumulating evidence has revealed that radiotherapy resistance is usually acquired soon after the treatment, and the corresponding additional irradiation dose often leads to unacceptable toxicity [ 24 , 25 ]. It is urgent for researchers to identify the regulatory mechanism for the metastasis of SCLC cells and reveal the molecular mechanisms underlying acquired radiotherapy resistance.…”

EGFR transcriptionally upregulates UTX via STAT3 in non-small cell lung cancer

“…However, the carcinogenic mutation of EGFR will lead to the continuous Lin Zhou and Xiaomu Wang have contributed equally to this work. activation of autophosphorylation, which can stimulate the abnormal proliferation of cells and lead to the occurrence and development of tumors (Liu et al 2019). Tyrosine kinase inhibitor (TKI) can effectively block the kinase domain of EGFR and has a promising therapeutic effect on NSCLC with EGFR activating mutation.…”

“…When EGFR binds to its specific ligand, it forms a dimer, which leads to autophosphorylation and activation of classical downstream signaling pathways of EGFR, including RAS/MAPK, PI3K/AKT and JAK/STAT3, thus promoting cell proliferation and avoiding apoptosis (Guo et al 2015 ; Roskoski 2014 ). However, the carcinogenic mutation of EGFR will lead to the continuous activation of autophosphorylation, which can stimulate the abnormal proliferation of cells and lead to the occurrence and development of tumors (Liu et al 2019 ). Tyrosine kinase inhibitor (TKI) can effectively block the kinase domain of EGFR and has a promising therapeutic effect on NSCLC with EGFR activating mutation.…”