EGFR tyrosine kinase inhibitors versus cranial radiation therapy for EGFR mutant non-small cell lung cancer with brain metastases: a systematic review and meta-analysis

Abstract

Background and purpose: EGFR TKIs alone have demonstrated activity against intracranial disease in EGFR mutant non-small cell lung cancer (NSCLC). This study aimed to determine if upfront cranial radiotherapy improves intracranial disease control and survival outcomes in EGFR mutant NSCLC with brain metastases relative to TKIs alone.

Materials and methods: We searched MEDLINE and various conference proceedings from 2008 to July 2014 for eligible studies where patients received upfront cranial radiotherapy or TKIs alone. Outcomes of interest were overall intracranial disease response rate (ORR), four-month intracranial disease progression-free survival (PFS), two-year overall survival (OS) and neurological adverse events (AE). We used random effects models to pool outcomes across studies and compared them using interaction tests.

Results: We found 12 non-comparative observational studies (n=363) with severe methodological limitations. Upfront cranial radiotherapy results in similar intracranial disease ORR (relative risk (RR) 0.93, 95% confidence interval (CI) 0.82-1.06; interaction p value (p)=0.53), improved four-month intracranial disease PFS (RR 1.06, 95% CI 1.00-1.12; p=0.03), improved two-year OS (RR 1.33, 95% CI 1.00-1.77; p=0.05) but caused more neurological AEs than TKIs alone.

Conclusion: There is evidence, albeit of low quality, that upfront cranial radiotherapy may improve intracranial disease control and survival outcomes compared with TKI alone.

Keywords: Epidermal growth factor receptor tyrosine kinase inhibitors; Non-small cell lung cancer; Stereotactic radiation therapy; Whole brain radiation therapy.