Neuro Oncol. 2015 Jun 30. pii: nov104. [Epub ahead of print]

Randomized phase 2 study of carboplatin and bevacizumab in recurrent glioblastoma.

Field KM1, Simes J1, Nowak AK1, Cher L1, Wheeler H1, Hovey EJ1, Brown CS1, Barnes EH1, Sawkins K1, Livingstone A1, Freilich R1, Phal PM1, Fitt G1; CABARET/COGNO investigators, Rosenthal MA1.

 

Author information:

1Royal Melbourne Hospital, Parkville, Australia (K.M.F, P.M.P, M.A.R.), National Health and Medical Research Council Clinical Trials Centre, University of Sydney, Sydney, Australia (J.S., C.S.B.B., E.H.B, K.S., A.L.); Sir Charles Gairdner Hospital, Nedlands, Australia (A.K.N); School of Medicine and Pharmacology, University of Western Australia, Crawley, Australia (A.K.N); Austin Health, Heidelberg, Australia (L.C., G.F.); Royal North Shore Hospital, St Leonards, Australia (H.W.); Prince of Wales Hospital, Randwick, Australia (E.J.H); University of New South Wales, Sydney, Australia (E.J.H); Monash Medical Centre, Clayton, Australia (R.F.); Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Parkville, Australia (P.M.P., M.A.R., G.F.).

 

Abstract

BACKGROUND:

 

The optimal use of bevacizumab in recurrent glioblastoma (GBM), including the choice of monotherapy or combination therapy, remains uncertain. The purpose of this study was to compare combination therapy with bevacizumab monotherapy.

METHODS:

 

This was a 2-part randomized phase 2 study. Eligibility criteria included recurrent GBM after radiotherapy and temozolomide, no other chemotherapy for GBM, and Eastern Cooperative Oncology Group performance status 0-2. The primary objective (Part 1) was to determine the effect of bevacizumab plus carboplatin versus bevacizumab monotherapy on progression-free survival (PFS) using modified Response Assessment in Neuro-Oncology criteria. Bevacizumab was given every 2 weeks, 10 mg/kg; and carboplatin every 4 weeks, (AUC 5). On progression, patients able to continue were randomized to continue or cease bevacizumab (Part 2). Secondary endpoints included objective radiological response rate (ORR), quality of life, toxicity, and overall survival (OS).

RESULTS:

 

One hundred twenty-two patients (median age, 55y) were enrolled to Part 1 from 18 Australian sites. Median follow-up was 32 months, and median on-treatment time was 3.3 months. Median PFS was 3.5 months for each arm (hazard ratio [HR]: 0.92, 95% CI: 0.64-1.33, P = .66). ORR was 14% (combination) versus 6% (monotherapy) (P = .18). Median OS was 6.9 (combination) versus 7.5 months (monotherapy) (HR: 1.18, 95% CI: 0.82-1.69, P = .38). The incidence of bevacizumab-related adverse events was similar to prior literature, with no new toxicity signals. Toxicities were higher in the combination arm. Part 2 data (n = 48) will be reported separately.

CONCLUSIONS:

 

Adding carboplatin resulted in more toxicity without additional clinical benefit. Clinical outcomes in patients with recurrent GBM treated with bevacizumab were inferior to those in previously reported studies.

CLINICAL TRIALS REGISTRATION NR:

 

ACTRN12610000915055.

 

© The Author(s) 2015. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.