Validation of diffusion MRI as a biomarker for efficacy using randomized phase III trial of bevacizumab with or without VB-111 in recurrent glioblastoma.

Background: Evidence from single and multicenter phase II trials have suggested diffusion MRI is a predictive imaging biomarker for survival benefit in recurrent glioblastoma (rGBM) treated with anti-VEGF therapy. The current study confirms these findings in a large, randomized phase III clinical trial.

Methods: Patients with rGBM were enrolled in a phase III randomized (1:1), controlled trial (NCT02511405) to compare the efficacy and safety of bevacizumab (BV) versus BV in combination with ofranergene obadenovec (BV+VB-111), an anti-cancer viral therapy. In 170 patients with diffusion MRI available, pretreatment enhancing tumor volume and ADC histogram analysis were used to phenotype patients as having high (>1.24 µm/ms) or low (<1.24 µm/ms) ADC, the mean value of the lower peak of the ADC histogram, within the contrast enhancing tumor.

Results: Baseline tumor volume ( = .3460) and ADC ( = .2143) did not differ between treatment arms. Univariate analysis showed patients with high ADC had a significant survival advantage in all patients ( = .0006), as well as BV ( = .0159) and BV+VB-111 individually ( = .0262). Multivariable Cox regression accounting for treatment arm, age, baseline tumor volume, and ADC identified continuous measures of tumor volume ( < .0001; HR = 1.0212) and ADC phenotypes ( = .0012; HR = 0.5574) as independent predictors of OS.

Conclusion: Baseline diffusion MRI and tumor volume are independent imaging biomarkers of OS in rGBM treated with BV or BV+VB-111.