Patterns of progression in patients with recurrent glioblastoma treated with bevacizumab.

Abstract

We evaluated patterns of tumor progression in patients with recurrent glioblastoma who were treated with bevacizumab (BEV) alone or in combination with irinotecan (CPT-11) while participating in the BRAIN study. An independent neuroradiologist reviewed MRI scans at baseline and progression in patients who received BEV (n = 85) or BEV+CPT-11 (n = 82) while on BRAIN. Tumor patterns were scored as local, distant, diffuse, or multifocal. Median progression-free survival (PFS) and overall survival (OS) were estimated using Kaplan-Meier methods. Hazard ratios for PFS and OS were estimated using a Cox regression model. Twenty-eight percent of patients who participated in BRAIN had nonlocal disease at baseline (72% local disease). Sixty-seven (79%) patients treated with single-agent BEV and 57 (70%) patients treated with BEV+CPT-11 experienced disease progression while on BRAIN. Most patients in each treatment group did not have a change in the radiographic pattern of their tumor (i.e., "no shift") at the time of progression. The proportion of BEV patients with no shift (82%) was greater than that of BEV+CPT-11 patients (53%, χ(2) p = 0.0004), and a greater proportion of BEV+CPT-11 patients (39%) compared with BEV patients (16%) experienced local-to-diffuse tumor pattern at progression (χ(2) p = 0.002). Patients treated with BEV or BEV+CPT-11 who had local-to-local or local-to-diffuse progression patterns had similar efficacy outcomes, including objective response, PFS, and OS. Most patients treated with BEV or BEV+CPT-11 on BRAIN did not experience a change from baseline in radiographic characteristics of disease at the time of progression.