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


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.


CONCLUSIONS
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.
Tracy T. Batchelor, Rakesh K. Jain, and Gregory Sorensen, Massachusetts General Hospital, Boston, MA; Paul Mulholland, University College London, London; Rao Gattamaneni, the Christie Foundation Trust Hospital, Manchester, United Kingdom; Bart Neyns, Universitair Ziekenhuis Brussel, Brussels, Belgium; L. Burt Nabors, University of Alabama at Birmingham, Birmingham, AL; Mario Campone, Centre Rene Gauducheau, Saint-Herblain, France; Antje Wick, University of Heidelberg, Heidelberg, Germany; Warren Mason, Princess Margaret Hospital, Toronto, Ontario, Canada; Tom Mikkelsen, Henry Ford Hospital, Detroit, MI; Surasak Phuphanich, Cedars-Sinai Medical Center, Los Angeles, CA; Lynn S. Ashby, Barrow Neurological Institute, Phoenix, AZ; John DeGroot, MD Anderson Cancer Center, Houston, TX; Lawrence Cher, Austin Health Cancer Services; Mark Rosenthal, Royal Melbourne Hospital, Melbourne, Australia; Franz Payer, Medical University, Graz, Austria; Juliane M. Jürgensmeier, John Xu, and Qi Liu, AstraZeneca, Wilmington, DE; and Martin van den Bent, Erasmus University Medical Center-Daniel den Hoed Cancer Center, Rotterdam, the Netherlands.
Tracy T
TT
Batchelor
Paul
P
Mulholland
Bart
B
Neyns
L Burt
LB
Nabors
Mario
M
Campone
Antje
A
Wick
Warren
W
Mason
Tom
T
Mikkelsen
Surasak
S
Phuphanich
Lynn S
LS
Ashby
John
J
Degroot
Rao
R
Gattamaneni
Lawrence
L
Cher
Mark
M
Rosenthal
Franz
F
Payer
Juliane M
JM
Jürgensmeier
Rakesh K
RK
Jain
A Gregory
AG
Sorensen
John
J
Xu
Qi
Q
Liu
Martin
M
van den Bent
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000401:mortality; D005260:Female; D005500:Follow-Up Studies; D005909:Glioblastoma / Q000188:drug therapy* / Q000401:mortality; D006801:Humans; D007390:International Agencies; D008130:Lomustine / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000401:mortality; D011379:Prognosis; D011799:Quinazolines / Q000008:administration & dosage; D015996:Survival Rate; D007211:Indoles
D008130:Lomustine; D011799:Quinazolines; C500926:cediranib; D007211:Indoles