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

Publication ,  Journal Article
Ellingson, BM; Aftab, DT; Schwab, GM; Hessel, C; Harris, RJ; Woodworth, DC; Leu, K; Chakhoyan, A; Raymond, C; Drappatz, J; de Groot, J ...
Published in: Neuro Oncol
September 3, 2018

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.

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Published In

Neuro Oncol

DOI

EISSN

1523-5866

Publication Date

September 3, 2018

Volume

20

Issue

10

Start / End Page

1411 / 1418

Location

England

Related Subject Headings

  • Young Adult
  • Tumor Burden
  • Survival Rate
  • Retrospective Studies
  • Pyridines
  • Protein Kinase Inhibitors
  • Prognosis
  • Oncology & Carcinogenesis
  • Neoplasm Recurrence, Local
  • Middle Aged
 

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Ellingson, B. M., Aftab, D. T., Schwab, G. M., Hessel, C., Harris, R. J., Woodworth, D. C., … Cloughesy, T. F. (2018). Volumetric response quantified using T1 subtraction predicts long-term survival benefit from cabozantinib monotherapy in recurrent glioblastoma. Neuro Oncol, 20(10), 1411–1418. https://doi.org/10.1093/neuonc/noy054
Ellingson, Benjamin M., Dana T. Aftab, Gisela M. Schwab, Colin Hessel, Robert J. Harris, Davis C. Woodworth, Kevin Leu, et al. “Volumetric response quantified using T1 subtraction predicts long-term survival benefit from cabozantinib monotherapy in recurrent glioblastoma.Neuro Oncol 20, no. 10 (September 3, 2018): 1411–18. https://doi.org/10.1093/neuonc/noy054.
Ellingson BM, Aftab DT, Schwab GM, Hessel C, Harris RJ, Woodworth DC, et al. Volumetric response quantified using T1 subtraction predicts long-term survival benefit from cabozantinib monotherapy in recurrent glioblastoma. Neuro Oncol. 2018 Sep 3;20(10):1411–8.
Ellingson, Benjamin M., et al. “Volumetric response quantified using T1 subtraction predicts long-term survival benefit from cabozantinib monotherapy in recurrent glioblastoma.Neuro Oncol, vol. 20, no. 10, Sept. 2018, pp. 1411–18. Pubmed, doi:10.1093/neuonc/noy054.
Ellingson BM, Aftab DT, Schwab GM, Hessel C, Harris RJ, Woodworth DC, Leu K, Chakhoyan A, Raymond C, Drappatz J, de Groot J, Prados MD, Reardon DA, Schiff D, Chamberlain M, Mikkelsen T, Desjardins A, Holland J, Ping J, Weitzman R, Wen PY, Cloughesy TF. Volumetric response quantified using T1 subtraction predicts long-term survival benefit from cabozantinib monotherapy in recurrent glioblastoma. Neuro Oncol. 2018 Sep 3;20(10):1411–1418.
Journal cover image

Published In

Neuro Oncol

DOI

EISSN

1523-5866

Publication Date

September 3, 2018

Volume

20

Issue

10

Start / End Page

1411 / 1418

Location

England

Related Subject Headings

  • Young Adult
  • Tumor Burden
  • Survival Rate
  • Retrospective Studies
  • Pyridines
  • Protein Kinase Inhibitors
  • Prognosis
  • Oncology & Carcinogenesis
  • Neoplasm Recurrence, Local
  • Middle Aged