Lessons learned from contemporary glioblastoma randomized clinical trials through systematic review and network meta-analysis: Part 2 recurrent glioblastoma

Abstract

Background. There exists no consensus standard of treatment for patients with recurrent glioblastoma (GB). Here we used a network meta-analysis on treatments from randomized control trials (RCTs) to assess the effect on overall survival (OS) and progression-free survival (PFS) to determine if any consensus treatment can be determined for recurrent GB. Methods. We included all recurrent GB RCTs with at least 20 patients in each arm, and for whom patients underwent standard of care at the time of their GB initial diagnosis. Our primary outcome was OS, with secondary outcomes including PFS and adverse reactions. Hazard ratio (HR) and its 95% confidence interval (CI) of the comparison of study arms regarding OS and PFS were extracted from each paper. For comparative efficacy analysis, we utilized a frequentist network meta-analysis, an extension of the classic pair-wise meta-analysis. We followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses. Results. Fifteen studies were included representing 29 separate treatment arms and 2194 patients. In our network meta-analysis, combination treatment with tumor-treating field and Vascular endothelial growth factor (VEGF) inhibitor ranked first in improving OS (P = .80). Concomitant anti-VEGF and Lomustine treatment was superior to Lomustine alone for extending PFS (HR 0.57, 95% CI 0.41-0.79) and ranked first in improving PFS compared to other included treatments (P = .86). Conclusions. Our analysis highlights the numerous studies performed on recurrent GB, with no proven consensus treatment that is superior to the current SOC. Intertrial heterogeneity precludes drawing strong conclusions, and confidence analysis was low to very low. Further confirmation by future trials is recommended for our exploratory results.