NRG/RTOG 0837: Randomized, phase II, double-blind, placebo-controlled trial of chemoradiation with or without cediranib in newly diagnosed glioblastoma.

Autor:	Batchelor TT; Department of Neurology, Brigham and Women's Hospital, Boston, Massachusetts, USA., Won M; Department of Statistics, NRG Oncology Statistics and Data Management Center, Philadelphia, Pennsylvania, USA., Chakravarti A; Department of Radiation Oncology, Wexner Medical Center, Ohio State University Comprehensive Cancer Center, Columbus, Ohio, USA., Hadjipanayis CG; Department of Neuro-Oncology, Neurosurgery, University of Pittsburgh Medical Center, Pittsburg, Pennsylvania, USA., Shi W; Department of Radiation Oncology, Thomas Jefferson University Hospital, Philadelphia, Pennsylvania, USA., Ashby LS; Department of Neurology, Barrow Neurological Institute, Phoenix, Arizona, USA., Stieber VW; Department of Radiation Oncology, Novant Health Forsyth Medical Center, Winston-Salem, North Carolina, USA., Robins HI; Department of Medicine, School of Medicine and Public Health, University of Wisconsin, Madison, Wisconsin, USA., Gray HJ; Department of Obstetrics and Gynecology, University of Washington Medical Center, Seattle, Washington, USA., Voloschin A; Department of Neuro-Oncology, Orlando Health Cancer Institute, Orlando, Florida, USA., Fiveash JB; Department of Radiation Oncology, University of Alabama at Birmingham Medical Center, Birmingham, Alabama, USA., Robinson CG; Department of Radiation Oncology, Washington University, St. Louis, Missouri, USA., Chamarthy U; Department of Medical Oncology/Hematology, Sparrow HH Cancer Center, Lansing, Michigan, USA., Kwok Y; Department of Radiation Oncology, University of Maryland Medical Systems, Baltimore, Maryland, USA., Cescon TP; Department of Hematology, Reading Hospital, Reading, Pennsylvania, USA., Sharma AK; Department of Radiation Oncology, Medical University of South Carolina, Charleston, South Carolina, USA., Chaudhary R; Department of Hematology Oncology, University of Cincinnati, Cincinnati, Ohio, USA., Polley MY; Department of Statistics, NRG Oncology Statistics and Data Management Center, Philadelphia, Pennsylvania, USA.; Department of Statistics, University of Chicago, Chicago, Illinois, USA., Mehta MP; Department of Radiation Oncology, Miami Cancer Institute, Miami, Florida, USA (M.P.M.).
Jazyk:	angličtina
Zdroj:	Neuro-oncology advances [Neurooncol Adv] 2023 Oct 11; Vol. 5 (1), pp. vdad116. Date of Electronic Publication: 2023 Oct 11 (Print Publication: 2023).
DOI:	10.1093/noajnl/vdad116
Abstrakt:	Background: A randomized, phase II, placebo-controlled, and blinded clinical trial (NCT01062425) was conducted to determine the efficacy of cediranib, an oral pan-vascular endothelial growth factor receptor tyrosine kinase inhibitor, versus placebo in combination with radiation and temozolomide in newly diagnosed glioblastoma. Methods: Patients with newly diagnosed glioblastoma were randomly assigned 2:1 to receive (1) cediranib (20 mg) in combination with radiation and temozolomide; (2) placebo in combination with radiation and temozolomide. The primary endpoint was 6-month progression-free survival (PFS) based on blinded, independent radiographic assessment of postcontrast T1-weighted and noncontrast T2-weighted MRI brain scans and was tested using a 1-sided Z test for 2 proportions. Adverse events (AEs) were evaluated per CTCAE version 4. Results: One hundred and fifty-eight patients were randomized, out of which 9 were ineligible and 12 were not evaluable for the primary endpoint, leaving 137 eligible and evaluable. 6-month PFS was 46.6% in the cediranib arm versus 24.5% in the placebo arm ( P  = .005). There was no significant difference in overall survival between the 2 arms. There was more grade ≥ 3 AEs in the cediranib arm than in the placebo arm ( P  = .02). Conclusions: This study met its primary endpoint of prolongation of 6-month PFS with cediranib in combination with radiation and temozolomide versus placebo in combination with radiation and temozolomide. There was no difference in overall survival between the 2 arms. Competing Interests: Dr Chakravarti, Ashby, Robins, Gray, Voloschin, Chamarthy, Kwok, Cescon, Sharma, Chaudhary, Polley and Ms Won have nothing to disclose. Dr Batchelor reports grants from AstraZeneca and Pfizer for support of clinical trials; personal fees from Merck for lectures, NXDC, Amgen, Roche, Oxigene, Proximagen/Usher, Genomicare, and Champions Biotechnology for scientific advisory board outside the submitted work; other potentially influencing activities, which are CME lectures Oakstone Medical Publishing, Oncology Audio Digest, Research To Practice, and Imedex, Editorial Board of UpToDate, Inc, and consulting in Jiahui Health, Consulting. Dr Hadjipanayis reports royalties from NX Development Corporation, and consulting in Synaptive Medical. Dr Shi reports grants from Regeneron for research funding; grants and personal fees from Novocure for research funding and consulting; personal fees from Brainlab, and Varian for consulting. Dr Stieber reports personal fees from Novocure for the speaker’s bureau. Dr Fiveash reports grants and others from Varian for consulting research and educational contracts. Dr Robinson reports grants and personal fees from Varian for MRA, grants for personal projects and consulting; grants from Elekta for personal projects; and equity from Radialogica. Dr Mehta reports personal fees from Karyopharm, Tocagen, AstraZeneca, Blue Earth, Celgene, and Abbvie for consulting, and Oncoceutics for the board of directors. (© The Author(s) 2023. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology.)
Databáze:	MEDLINE
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