Brown, N., McBain, C., Nash, S., Hopkins, K., Sanghera, P., Saran, F., Phillips, M., Dungey, F., Clifton-Hadley, L., Wanek, K., Krell, D., Jeffries, S., Khan, I., Smith, P., Mulholland, P. (2016) Multi-Center Randomized Phase II Study Comparing Cediranib plus Gefitinib with Cediranib plus Placebo in Subjects with Recurrent/Progressive Glioblastoma. PLOS ONE, 11 (5). ISSN 1932-6203

Preview

Text 15151.pdf Download (1MB) | Preview

Abstract

Background Cediranib, an oral pan-vascular endothelial growth factor (VEGF) receptor tyrosine kinase inhibitor, failed to show benefit over lomustine in relapsed glioblastoma. One resistance mechanism for cediranib is up-regulation of epidermal growth factor receptor (EGFR). This study aimed to determine if dual therapy with cediranib and the oral EGFR inhibitor gefitinib improved outcome in recurrent glioblastoma. Methods and Findings This was a multi-center randomized, two-armed, double-blinded phase II study comparing cediranib plus gefitinib versus cediranib plus placebo in subjects with first relapse/first progression of glioblastoma following surgery and chemoradiotherapy. The primary outcome measure was progression free survival (PFS). Secondary outcome measures included overall survival (OS) and radiologic response rate. Recruitment was terminated early following suspension of the cediranib program. 38 subjects (112 planned) were enrolled with 19 subjects in each treatment arm. Median PFS with cediranib plus gefitinib was 3.6 months compared to 2.8 months for cediranib plus placebo (HR; 0.72, 90% CI; 0.41 to 1.26). Median OS was 7.2 months with cediranib plus gefitinib and 5.5 months with cediranib plus placebo (HR; 0.68, 90% CI; 0.39 to 1.19). Eight subjects (42%) had a partial response in the cediranib plus gefitinib arm versus five patients (26%) in the cediranib plus placebo arm. Conclusions Cediranib and gefitinib in combination is tolerated in patients with glioblastoma. Incomplete recruitment led to the study being underpowered. However, a trend towards improved survival and response rates with the addition of gefitinib to cediranib was observed. Further studies of the combination incorporating EGFR and VEGF inhibition are warranted.

Item Type:	Article
All Authors:	Brown, N., McBain, C., Nash, S., Hopkins, K., Sanghera, P., Saran, F., Phillips, M., Dungey, F., Clifton-Hadley, L., Wanek, K., Krell, D., Jeffries, S., Khan, I., Smith, P., Mulholland, P.
Additional Information:	ISI Document Delivery No.: DN2GV Times Cited: 0 Cited Reference Count: 50 Brown, Nicholas McBain, Catherine Nash, Stephen Hopkins, Kirsten Sanghera, Paul Saran, Frank Phillips, Mark Dungey, Fiona Clifton-Hadley, Laura Wanek, Katharina Krell, Daniel Jeffries, Sarah Khan, Iftekhar Smith, Paul Mulholland, Paul Astra Zeneca; Cancer Research UK [E/10/044]; National Institute of Health Research/Wellcome University College Hospital (NIHR/UCH) Clinical Research Facility; University College Hospital/University College London (UCH/UCL) Biomedical Research Centre; UCL Experimental Cancer Medicine Centre; National Brain Appeal This study was supported by Astra Zeneca, Cancer Research UK E/10/044, the National Institute of Health Research/Wellcome University College Hospital (NIHR/UCH) Clinical Research Facility, the University College Hospital/University College London (UCH/UCL) Biomedical Research Centre and UCL Experimental Cancer Medicine Centre, and the National Brain Appeal. www.astrazeneca.co.uk, www.cancerresearchuk.org, www.uclh.nhs.uk/Research/CRF, www.uclhospitals.brc.nihr.ac.uk, www.ecmcnetwork.org.uk/network-centres/london-ucl, www.nationalbrainappeal.org. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. 0 PUBLIC LIBRARY SCIENCE SAN FRANCISCO PLOS ONE
Uncontrolled Keywords:	GROWTH-FACTOR-RECEPTOR TYROSINE KINASE INHIBITOR HIGH-GRADE GLIOMAS HUMAN CANCER-CELLS RECURRENT GLIOBLASTOMA BRAIN-TUMORS ADJUVANT TEMOZOLOMIDE ACQUIRED-RESISTANCE PROGNOSTIC-FACTORS MALIGNANT GLIOMA
Research teams:	Clinical Units > Neuro-oncology Unit
Depositing User:	Barry Jenkins
Date Deposited:	27 Jun 2016 12:44
Last Modified:	27 Jun 2016 12:49
URI:	http://publications.icr.ac.uk/id/eprint/15151

Actions (login required)

View Item