Volumetric response quantified using T1 subtraction predicts long-term survival benefit from cabozantinib monotherapy in recurrent glioblastoma.

Abstract

Background:

To overcome challenges with traditional response assessment in anti-angiogenic agents, the current study uses T1 subtraction maps to quantify volumetric radiographic response in monotherapy with cabozantinib, an orally bioavailable tyrosine kinase inhibitor with activity against vascular endothelial growth factor receptor 2 (VEGFR2), hepatocyte growth factor receptor (MET), and AXL, in an open-label, phase II trial in patients with recurrent glioblastoma (GBM) (NCT00704288).

Methods:

A total of 108 patients with adequate imaging data and confirmed recurrent GBM were included in this retrospective study from a phase II multicenter trial of cabozantinib monotherapy (XL184-201) at either 100 mg (N = 87) or 140 mg (N = 21) per day. Contrast enhanced T1-weighted digital subtraction maps were used to define volume of contrast-enhancing tumor at baseline and subsequent follow-up time points. Volumetric radiographic response (>65% reduction in contrast-enhancing tumor volume from pretreatment baseline tumor volume sustained for more than 4 wk) was tested as an independent predictor of overall survival (OS).

Results:

Volumetric response rate for all therapeutic doses was 38.9% (41.4% and 28.6% for 100 mg and 140 mg doses, respectively). A log-linear association between baseline tumor volume and OS (P = 0.0006) and a linear correlation between initial change in tumor volume and OS (P = 0.0256) were observed. A significant difference in OS was observed between responders (median OS = 20.6 mo) and nonresponders (median OS = 8.0 mo) (hazard ratio [HR] = 0.3050, P < 0.0001). Multivariable analyses showed that continuous measures of baseline tumor volume (HR = 1.0233, P < 0.0001) and volumetric response (HR = 0.2240, P < 0.0001) were independent predictors of OS.

Conclusions:

T1 subtraction maps provide value in determining response in recurrent GBM treated with cabozantinib and correlated with survival benefit.

• Authors: Benjamin M Ellingson, Dana T Aftab, Gisela M Schwab, Colin Hessel, Robert J Harris, Davis C Woodworth, Kevin Leu, Ararat Chakhoyan, Catalina Raymond, Jan Drappatz, John de Groot, Michael D Prados, David A Reardon, David Schiff, Marc Chamberlain, Tom Mikkelsen, Annick Desjardins, Jaymes Holland, Jerry Ping, Ron Weitzman, Patrick Y Wen, Timothy F Cloughesy
• Journal: Neuro-oncology (Neuro Oncol) Vol. 20 Issue 10 Pg. 1411-1418 (09 03 2018) ISSN: 1523-5866 [Electronic] England
• PMID: 29660005 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Anilides
• Contrast Media
• Protein Kinase Inhibitors
• Pyridines
• cabozantinib

Topics

• Adult
• Aged
• Anilides (therapeutic use)
• Brain Neoplasms (diagnostic imaging, drug therapy, mortality, pathology)
• Contrast Media
• Female
• Follow-Up Studies
• Glioblastoma (diagnostic imaging, drug therapy, mortality, pathology)
• Humans
• Magnetic Resonance Imaging (methods)
• Male
• Middle Aged
• Neoplasm Recurrence, Local (diagnostic imaging, drug therapy, mortality, pathology)
• Prognosis
• Protein Kinase Inhibitors (therapeutic use)
• Pyridines (therapeutic use)
• Retrospective Studies
• Survival Rate
• Tumor Burden
• Young Adult