Field, KM and Simes, J and Nowak, AK and Cher, L and Wheeler, H and Hovey, EJ and Brown, CSB and Barnes, EH and Sawkins, K and Livingstone, A and Freilich, R and Phal, PM and Fitt, G and Rosenthal, MA and Arzhintar, I and Garrett, L and Byrne, A and Dowling, A and Ranieri, N and Jennens, R and Osmond, F and Patterson, WK and Phay, A and Abell, F and Plowman, L and Flynn, J and Hovey, E and Kilsby, H and Wheeler, H and Kirby-Lewis, S and Singhal, N and Smith, S and Whelan, M and Inglis, P and Ives, A and Nowak, A and Lobb, S and Begbie, S and Williams, P and Lwin, Z and Woodward, N and Crosbie, G and Harrup, R and Pyszkowski, L and Gauden, S and Neville, A, Randomized phase 2 study of carboplatin and bevacizumab in recurrent glioblastoma, Neuro-Oncology, 17, (11) pp. 1504-1513. ISSN 1522-8517 (2015) [Refereed Article]
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 = 0.. 66). ORR was 14% (combination) versus 6% (monotherapy) (P = 0. 18). Median OS was 6.9 (combination) versus 7.5 months (monotherapy) (HR: 1.18, 95% CI: 0.82-1.69, (P = 0.. 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.
|Item Type:||Refereed Article|
|Keywords:||bevacizumab, carboplatin, glioblastoma|
|Research Division:||Medical and Health Sciences|
|Research Group:||Pharmacology and Pharmaceutical Sciences|
|Research Field:||Clinical Pharmacology and Therapeutics|
|Objective Group:||Clinical Health (Organs, Diseases and Abnormal Conditions)|
|Objective Field:||Cancer and Related Disorders|
|Author:||Harrup, R (Dr Rosemary Harrup)|
|Author:||Gauden, S (Dr Stan Gauden)|
|Author:||Neville, A (Mrs Alexandra Neville)|
|Web of Science® Times Cited:||11|
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