Volumetric response quantified using T1 subtraction predicts long-term survival benefit from cabozantinib monotherapy in recurrent glioblastoma
| Autor: | Ron Weitzman, Davis C. Woodworth, Colin Hessel, Jaymes Holland, Patrick Y. Wen, Dana T. Aftab, Michael D. Prados, John de Groot, Ararat Chakhoyan, Catalina Raymond, Jan Drappatz, Jerry Ping, Annick Desjardins, Timothy F. Cloughesy, David Schiff, Gisela Schwab, Robert J. Harris, David A. Reardon, Marc C. Chamberlain, Kevin Leu, Benjamin M. Ellingson, Tom Mikkelsen |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Male Cancer Research Pyridines Contrast Media Tyrosine-kinase inhibitor chemistry.chemical_compound 0302 clinical medicine Medicine Anilides Cancer Brain Neoplasms Hazard ratio Subtraction Middle Aged Prognosis Magnetic Resonance Imaging Tumor Burden Survival Rate Oncology Local 030220 oncology & carcinogenesis 6.1 Pharmaceuticals Female recurrent glioblastoma Adult medicine.medical_specialty Cabozantinib medicine.drug_class Clinical Trials and Supportive Activities Oncology and Carcinogenesis Urology Neuroimaging GBM 03 medical and health sciences Young Adult Rare Diseases cabozantinib Clinical Research Multicenter trial Long term survival Humans Oncology & Carcinogenesis Survival rate Protein Kinase Inhibitors Aged Retrospective Studies business.industry T1 subtraction Recurrent glioblastoma Neurosciences Evaluation of treatments and therapeutic interventions Brain Disorders Brain Cancer 030104 developmental biology Neoplasm Recurrence chemistry XL184 Neurology (clinical) Neoplasm Recurrence Local business Glioblastoma Follow-Up Studies |
| Zdroj: | Neuro-oncology, vol 20, iss 10 Ellingson, BM; Aftab, DT; Schwab, GM; Hessel, C; Harris, RJ; Woodworth, DC; et al.(2018). Volumetric response quantified using T1 subtraction predicts long-term survival benefit from cabozantinib monotherapy in recurrent glioblastoma. NEURO-ONCOLOGY, 20(10), 1411-1418. doi: 10.1093/neuonc/noy054. UCLA: Retrieved from: http://www.escholarship.org/uc/item/66j537hb |
| ISSN: | 1523-5866 0070-4288 |
| DOI: | 10.1093/neuonc/noy054. |
| Popis: | Author(s): Ellingson, Benjamin M; Aftab, Dana T; Schwab, Gisela M; Hessel, Colin; Harris, Robert J; Woodworth, Davis C; Leu, Kevin; Chakhoyan, Ararat; Raymond, Catalina; Drappatz, Jan; de Groot, John; Prados, Michael D; Reardon, David A; Schiff, David; Chamberlain, Marc; Mikkelsen, Tom; Desjardins, Annick; Holland, Jaymes; Ping, Jerry; Weitzman, Ron; Wen, Patrick Y; Cloughesy, Timothy F | 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 (g65% 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 l 0.0001). Multivariable analyses showed that continuous measures of baseline tumor volume (HR = 1.0233, P l 0.0001) and volumetric response (HR = 0.2240, P l 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. |
| Databáze: | OpenAIRE |
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