Upfront Cranial Radiotherapy vs. EGFR Tyrosine Kinase Inhibitors Alone for the Treatment of Brain Metastases From Non-small-cell Lung Cancer: A Meta-Analysis of 1465 Patients

Xiao-Jing Du, Su-Ming Pan, Shu-Zhen Lai, Xiao-Nan Xu, Mei-Ling Deng, Xiao-Hui Wang, Dun-Chen Yao, Shao-Xiong Wu, Xiao-Jing Du, Su-Ming Pan, Shu-Zhen Lai, Xiao-Nan Xu, Mei-Ling Deng, Xiao-Hui Wang, Dun-Chen Yao, Shao-Xiong Wu

Abstract

Background: Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) is revolutionizing the management of brain metastases (BMs). This study was to explore the value of upfront cranial radiotherapy (RT) in EGFR-mutated non-small cell lung cancer (NSCLC) with BMs compared with EGFR-TKIs alone. Methods: We searched all topic-related comparative articles in public databases (MEDLINE, EMBASE, Cochrane Library, and Web of Science) and conference proceedings. Outcomes of interest were intracranial objective response rate (ORR), overall survival (OS), and intracranial progression-free survival (PFS). Statistical analyses were calculated using Review Manager 5.3 software. Results: Thirteen comparative studies that included a total of 1,456 patients were eligible. Upfront brain RT had significantly higher OS (HR = 0.78, 95% CI = 0.65-0.93, P = 0.005) than EGFR-TKI alone. Upfront RT plus TKI had superior OS (HR = 0.71, 95% CI = 0.58-0.86, P = 0.0005) and intracranial PFS (HR = 0.69, 95% CI = 0.49-0.99, P = 0.04). The pooled data favored upfront whole brain RT (WBRT) plus TKI in terms of intracranial PFS (HR = 0.64, 95% CI = 0.48-0.85, P = 0.002) and OS (HR = 0.75, 95% CI = 0.57-1, P = 0.05). Upfront stereotactic radiosurgery (SRS) was associated with better OS (HR = 0.37, 95% CI = 0.26-0.54, P < 0.00001). Similar results were observed when analysis was restricted to the use of erlotinib or geftinib. Conclusions: The upfront use of brain RT seemed critical, especially for SRS. Upfront administration of upfront WBRT plus EGFR-TKI had better survival outcomes and seemed superior to EGFR-TKI alone.

Keywords: epidermal growth factor receptor; non-small-cell lung cancer; stereotactic radiosurgery; tyrosine kinase inhibitors; whole brain radiation therapy.

Figures

Figure 1
Figure 1
Flowchart showing the selection of the trials.
Figure 2
Figure 2
Forest plot and meta-analysis of intracranial objective response rate (ORR) in subgroup analysis.
Figure 3
Figure 3
Forest plot and meta-analysis of overall survival (OS). RT, radiotherapy; WBRT, whole brain radiotherapy; SRS, stereotactic radiosurgery; TKI, tyrosine kinase inhibitor.
Figure 4
Figure 4
Forest plot and meta-analysis for upfront radiotherapy vs. erlotinib/geftinib alone. (A) Overall survival. (B) Intracranial progression-free survival. RT, radiotherapy; WBRT, whole brain radiotherapy.
Figure 5
Figure 5
Forest plot and meta-analysis of intacranial progression-free survival (PFS). (A) Pooled data based on random-effects model. (B) Pooled data based on fix-effect model. RT, radiotherapy; WBRT, whole brain radiotherapy; TKI, tyrosine kinase inhibitor.
Figure 6
Figure 6
Forest plot and meta-analysis of intacranial progression-free survival (PFS) f in patients with asymptomatic brain metastases. RT, radiotherapy; TKI, tyrosine kinase inhibitor.
Figure 7
Figure 7
Funnel plot for assessing publication bias of overall survival (OS) in overall meta-analysis.

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