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

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

Tracy T Batchelor  1 , Minhee Won  2 , Arnab Chakravarti  3 , Costas G Hadjipanayis  4 , Wenyin Shi  5 , Lynn S Ashby  6 , Volker W Stieber  7 , H Ian Robins  8 , Heidi J Gray  9 , Alfredo Voloschin  10 , John B Fiveash  11 , Clifford G Robinson  12 , UshaSree Chamarthy  13 , Young Kwok  14 , Terrence P Cescon  15 , Anand K Sharma  16 , Rekha Chaudhary  17 , Mei-Yin Polley  2   18 , Minesh P Mehta  19
Affiliations

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

Tracy T Batchelor et al. Neurooncol Adv. .

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.

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Conflict of interest statement

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.

Figures

Figure 1.
Figure 1.
CONSORT diagram.
Figure 2.
Figure 2.
Overall survival by treatment arm.
Figure 3.
Figure 3.
Progression-free survival by treatment arm.
See this image and copyright information in PMC

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