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Clinical Trial
. 2013 Sep 10;31(26):3212-8.
doi: 10.1200/JCO.2012.47.2464. Epub 2013 Aug 12.

Phase III randomized trial comparing the efficacy of cediranib as monotherapy, and in combination with lomustine, versus lomustine alone in patients with recurrent glioblastoma

Tracy T Batchelor  1 , Paul Mulholland, Bart Neyns, L Burt Nabors, Mario Campone, Antje Wick, Warren Mason, Tom Mikkelsen, Surasak Phuphanich, Lynn S Ashby, John Degroot, Rao Gattamaneni, Lawrence Cher, Mark Rosenthal, Franz Payer, Juliane M Jürgensmeier, Rakesh K Jain, A Gregory Sorensen, John Xu, Qi Liu, Martin van den Bent
Affiliations
Clinical Trial

Phase III randomized trial comparing the efficacy of cediranib as monotherapy, and in combination with lomustine, versus lomustine alone in patients with recurrent glioblastoma

Tracy T Batchelor et al. J Clin Oncol. .

Abstract

Purpose: A randomized, phase III, placebo-controlled, partially blinded clinical trial (REGAL [Recent in in Glioblastoma Alone and With Lomustine]) was conducted to determine the efficacy of cediranib, an oral pan-vascular endothelial growth factor (VEGF) receptor tyrosine kinase inhibitor, either as monotherapy or in combination with lomustine versus lomustine in patients with recurrent glioblastoma.

Patients and methods: Patients (N = 325) with recurrent glioblastoma who previously received radiation and temozolomide were randomly assigned 2:2:1 to receive (1) cediranib (30 mg) monotherapy; (2) cediranib (20 mg) plus lomustine (110 mg/m(2)); (3) lomustine (110 mg/m(2)) plus a placebo. The primary end point was progression-free survival based on blinded, independent radiographic assessment of postcontrast T1-weighted and noncontrast T2-weighted magnetic resonance imaging (MRI) brain scans.

Results: The primary end point of progression-free survival (PFS) was not significantly different for either cediranib alone (hazard ratio [HR] = 1.05; 95% CI, 0.74 to 1.50; two-sided P = .90) or cediranib in combination with lomustine (HR = 0.76; 95% CI, 0.53 to 1.08; two-sided P = .16) versus lomustine based on independent or local review of postcontrast T1-weighted MRI.

Conclusion: This study did not meet its primary end point of PFS prolongation with cediranib either as monotherapy or in combination with lomustine versus lomustine in patients with recurrent glioblastoma, although cediranib showed evidence of clinical activity on some secondary end points including time to deterioration in neurologic status and corticosteroid-sparing effects.

Trial registration: ClinicalTrials.gov NCT00777153.

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Conflict of interest statement

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

Figures

Fig 1.
Fig 1.
CONSORT diagram. ITT, intent to treat.
Fig 2.
Fig 2.
Progression-free survival (PFS; based on central review postcontrast T1). No. at risk denotes the number of patients who were event free at the beginning of the period. Ced, cediranib; HR, hazard ratio; lom, lomustine; Pla, placebo.
Fig 3.
Fig 3.
Overall survival (OS). No. at risk denotes the number of patients who were event free at the beginning of the period. Ced, cediranib; HR, hazard ratio; lom, lomustine; Pla, placebo.
Fig 4.
Fig 4.
Best change from baseline in contrast-enhancing area. (A) Cediranib; (B) cediranib plus lomustine; (C) placebo plus lomustine.
See this image and copyright information in PMC

Comment in

References

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