RT-based combination therapy for brain metastasis from NSCLC with non-EGFR mutation/ALK gene rearrangement: A network meta-analysis

INTRODUCTION: Radiotherapy (RT) is currently the main treatment for brain metastases (BMs) from non-small cell lung cancer (NSCLC). Due to the short survival time and obvious adverse reactions of RT, we urgently need more appropriate treatment. This network meta-analysis reviewed the efficacy and adverse effects of radiotherapy-based combination therapy for patients without targeted epidermal growth factor receptor (EGFR) mutations/anaplastic lymphoma kinase (ALK) gene rearrangement NSCLC BMs, to screen out the therapy with the best efficacy. METHODS: PubMed, Embase, Web of Science, and Cochrane Library were searched from the earliest publication date available to 1 April 2022. STATA15.0 was used to conduct heterogeneity analysis, sensitivity analysis, forest plot analysis, and publication bias analysis. RESULTS: A total of 28 studies, involving 3707 patients were included in the Bayesian network meta-analysis. In the limited paired meta-analysis for head-to-head comparative trials, compared with RT-based combination therapy, RT combined with Immune checkpoint inhibitors (ICIs) showed significant overall survival (OS) benefit (HR 0.65, 95%CI 0.47–0.9, p<0.01), RT combined with ICIs showed a non-significant difference for intracranial progression-free survival (iPFS) (HR 0.76, 95%CI 0.27–2.27, p<0.01) and progression-free survival (PFS) (HR 0.9, 95%CI 0.36–2.37, p<0.01). In addition, according to the ranking results, compared with RT combined with chemotherapy(CT) or with targeted therapy(TT), RT combined with ICIs might be the best treatment mode for OS(ICIs+RT vs CT+RT vs TT+RT; 91.9% vs. 27.8% vs. 29.3%, iPFS (ICIs+RT vs CT+RT vs TT+RT, 46.9% vs 25.2% vs 25.6%) and PFS (ICIs+RT vs CT+RT vs TT+RT, 36.2% vs 31% vs 36.5%). CONCLUSIONS: RT combined with ICIs might be the best treatment mode to prolong the OS for BMs from NSCLC with non-EGFR mutation/ALK gene rearrangement. REVIEW REGISTRATION: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022350065, identifier (CRD42022350065)