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

Benjamin M. Ellingson, Kunal Patel, Chencai Wang, Catalina Raymond, Andrew Brenner, John F. De Groot, Nicholas A. Butowski, Leor Zach, Jian L. Campian, Jacob Schlossman, Shan Rizvi, Yael C. Cohen, Noa Lowenton-Spier, Tamar Rachmilewitz Minei, Shifra Fain Shmueli, Patrick Y. Wen, Timothy F. Cloughesy

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

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 μm2/ms) or low (<1.24 μm2/ms) ADCL, the mean value of the lower peak of the ADC histogram, within the contrast enhancing tumor. Results. Baseline tumor volume (P = .3460) and ADCL (P = .2143) did not differ between treatment arms. Univariate analysis showed patients with high ADCLhad 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 ADCLidentified continuous measures of tumor volume (P < .0001; HR = 1.0212) and ADCLphenotypes (P = .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.

Original languageEnglish (US)
Article numbervdab082
JournalNeuro-Oncology Advances
Volume3
Issue number1
DOIs
StatePublished - Jan 1 2021
Externally publishedYes

Keywords

  • Anti-VEGF therapy
  • VB-111
  • bevacizumab
  • diffusion MRI
  • imaging biomarker
  • recurrent GBM

ASJC Scopus subject areas

  • Clinical Neurology
  • Oncology
  • Surgery

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