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

Tracy T Batchelor; Minhee Won; Arnab Chakravarti; Costas G Hadjipanayis; Wenyin Shi; Lynn S Ashby; Volker W Stieber; H Ian Robins; Heidi J Gray; Alfredo Voloschin; John B Fiveash; Clifford G Robinson; UshaSree Chamarthy; Young Kwok; Terrence P Cescon; Anand K Sharma; Rekha Chaudhary; Mei-Yin Polley; Minesh P Mehta

doi:10.1093/noajnl/vdad116

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

Neurooncol Adv. 2023 Oct 11;5(1):vdad116. doi: 10.1093/noajnl/vdad116. eCollection 2023 Jan-Dec.

Authors

Tracy T Batchelor¹, Minhee Won², Arnab Chakravarti³, Costas G Hadjipanayis⁴, Wenyin Shi⁵, Lynn S Ashby⁶, Volker W Stieber⁷, H Ian Robins⁸, Heidi J Gray⁹, Alfredo Voloschin¹⁰, John B Fiveash¹¹, Clifford G Robinson¹², UshaSree Chamarthy¹³, Young Kwok¹⁴, Terrence P Cescon¹⁵, Anand K Sharma¹⁶, Rekha Chaudhary¹⁷, Mei-Yin Polley^{2

18}, Minesh P Mehta¹⁹

Affiliations

¹ Department of Neurology, Brigham and Women's Hospital, Boston, Massachusetts, USA.
² Department of Statistics, NRG Oncology Statistics and Data Management Center, Philadelphia, Pennsylvania, USA.
³ Department of Radiation Oncology, Wexner Medical Center, Ohio State University Comprehensive Cancer Center, Columbus, Ohio, USA.
⁴ Department of Neuro-Oncology, Neurosurgery, University of Pittsburgh Medical Center, Pittsburg, Pennsylvania, USA.
⁵ Department of Radiation Oncology, Thomas Jefferson University Hospital, Philadelphia, Pennsylvania, USA.
⁶ Department of Neurology, Barrow Neurological Institute, Phoenix, Arizona, USA.
⁷ Department of Radiation Oncology, Novant Health Forsyth Medical Center, Winston-Salem, North Carolina, USA.
⁸ Department of Medicine, School of Medicine and Public Health, University of Wisconsin, Madison, Wisconsin, USA.
⁹ Department of Obstetrics and Gynecology, University of Washington Medical Center, Seattle, Washington, USA.
¹⁰ Department of Neuro-Oncology, Orlando Health Cancer Institute, Orlando, Florida, USA.
¹¹ Department of Radiation Oncology, University of Alabama at Birmingham Medical Center, Birmingham, Alabama, USA.
¹² Department of Radiation Oncology, Washington University, St. Louis, Missouri, USA.
¹³ Department of Medical Oncology/Hematology, Sparrow HH Cancer Center, Lansing, Michigan, USA.
¹⁴ Department of Radiation Oncology, University of Maryland Medical Systems, Baltimore, Maryland, USA.
¹⁵ Department of Hematology, Reading Hospital, Reading, Pennsylvania, USA.
¹⁶ Department of Radiation Oncology, Medical University of South Carolina, Charleston, South Carolina, USA.
¹⁷ Department of Hematology Oncology, University of Cincinnati, Cincinnati, Ohio, USA.
¹⁸ Department of Statistics, University of Chicago, Chicago, Illinois, USA.
¹⁹ Department of Radiation Oncology, Miami Cancer Institute, Miami, Florida, USA (M.P.M.).

Abstract

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.

Keywords: angiogenesis; cediranib; glioblastoma; vascular endothelial growth factor.

Abstract

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