Validation of diffusion MRI as a biomarker for efficacy using randomized phase III trial of bevacizumab with or...

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.

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 µm²/ms) or low (<1.24 µm²/ms) ADC_L, the mean value of the lower peak of the ADC histogram, within the contrast enhancing tumor.

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

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