Cancer Med. 2019 Nov 22. doi: 10.1002/cam4.2616. [Epub ahead of print]

Gleeson JP1,2, Keane F1, Keegan NM1,2, Mammadov E1, Harrold E1,3, Alhusaini A1,4, Harte J1,4, Eakin-Love A4, O'Halloran PJ5, MacNally S5, Hennessy BT1,4,6, Breathnach OS1,4,6, Grogan L1,4,6, Morris PG1,4,6.

 

Author information:

1. Medical Oncology Department, Beaumont Hospital, Dublin, Ireland.

2. Medical Oncology Department, Memorial Sloan Kettering Cancer Center, New York, NY, USA.

3. Medical Oncology Department, Mater Misericordiae University Hospital, Dublin, Ireland.

4. Royal College of Surgeons of Ireland (RCSI), Dublin, Ireland.

5. Neurosurgical Department, Beaumont Hospital, Dublin, Ireland.

6. Cancer Clinical Trials and Research Unit, RCSI Hospital Group, Beaumont Hospital, Dublin, Ireland.

Abstract

INTRODUCTION:

 

Bevacizumab has demonstrated activity in glioblastoma (GBM), but the true benefits and optimal dose-schedule are debated. A lower dose-schedule than standard-dose bevacizumab (10 mg/kg 2-weekly) might offer similar benefits with lower costs. At our Institution, patients are randomly assigned at time of primary diagnosis to Neuro-Oncologists, who have varying practices in terms of bevacizumab dose-schedule upon progression.

METHODS:

 

In a retrospective analysis we examined overall survival (OS), measured from first administered bevacizumab dose until death, according to dose-schedule. Patients with de novo WHO Grade IV GBM who received standard- or reduced-dose (5 mg/kg 2-weekly) bevacizumab were included. MGMT methylation status and time from diagnosis to bevacizumab start were examined as prognostic variables. Clinical benefit and a comparative cost analysis were assessed.

RESULTS:

 

In total, 1127 bevacizumab doses were administered to 118 patients [Median: 7, Range: 1-44]. Median OS (mOS) was 5.8 months. 69 (59%) patients received standard-dose bevacizumab (mOS: 5.97 months) and 49 patients received reduced-dose (mOS: 5.7 months). No statistically significant difference in OS between dosing schedule was seen (HR: 1.11, P-value: .584). Patients with MGMT methylated tumors (43%) had improved OS compared to those with unmethylated tumors; 7.03 vs 4.97 months (HR: 0.61, P-value: .027). If all patients were treated with reduced-dose bevacizumab, an estimated €2.4M cost reduction would be observed.

CONCLUSIONS:

 

In this retrospective study, reduced-dose bevacizumab schedule resulted in similar OS to standard-dose bevacizumab monotherapy with substantial cost savings. MGMT methylation appears to convey a survival benefit in the setting of bevacizumab treatment for progressive GBM.

 

© 2019 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.