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

• Published in: Neuro-oncology advances 2023-01, Vol.5 (1), p.vdad116-vdad116
• Main Authors: Batchelor, Tracy T, Won, Minhee, Chakravarti, Arnab, Hadjipanayis, Costas G, Shi, Wenyin, Ashby, Lynn S, Stieber, Volker W, Robins, H Ian, Gray, Heidi J, Voloschin, Alfredo, Fiveash, John B, Robinson, Clifford G, Chamarthy, UshaSree, Kwok, Young, Cescon, Terrence P, Sharma, Anand K, Chaudhary, Rekha, Polley, Mei-Yin, Mehta, Minesh P
• Format: Article
• Language: English
• ISSN: 2632-2498; 2632-2498
• DOI: 10.1093/noajnl/vdad116

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.