Neurocognitive function in patients with recurrent glioblastoma treated with bevacizumab

Abstract

Neurocognitive decline is a frequent adverse effect of glioblastoma. Antitumor therapies that are efficacious, as measured by traditional endpoints such as objective response (OR) and progression-free survival (PFS), and have beneficial effects on neurocognitive function (NCF) are of clinical benefit to these patients. We evaluated neurocognitive changes across time in 167 patients with recurrent glioblastoma treated with bevacizumab-based therapy in BRAIN, a phase II, randomized, multicenter trial. All patients underwent MRI and neurocognitive testing at baseline and every 6 weeks thereafter. Memory, visuomotor scanning speed, and executive function were evaluated using the Hopkins Verbal Learning Test-Revised, the Trail Making Test, and the Controlled Oral Word Association test, respectively. NCF relative to baseline for patients with an OR, PFS >6 months, or disease progression was evaluated at time of OR, 24 weeks, and time of progression, respectively. For patients with an OR or PFS >6 months, median standardized test scores were examined from baseline to week 24. Most patients with an OR or PFS >6 months had poorer NCF performance compared to the general population at baseline and had improved or stable NCF at the time of response or at the 24-week assessment, respectively; most patients with progressive disease had neurocognitive decline at the time of progression. For patients with an OR or PFS >6 months, median standardized test scores were largely stable across the first 24 weeks on study. Neurocognitive testing was an objective, valid, and feasible method of monitoring NCF in patients with recurrent glioblastoma.

Fig. 1.

Neurocognitive test scores across time for patients with an objective response. Values represent median test scores of patients in the BEV (upper panel) and BEV + CPT-11 (lower panel) study groups who had an IRF-determined objective response and completed neurocognitive tests at the indicated time of assessment, standardized using normative data from the general population (i.e., mean = 0, SD = 1). Values under the x-axis represent the number of patients assessed at each corresponding timepoint. BEV, bevacizumab; CPT-11, irinotecan; HVLT-R, Hopkins Verbal Learning Test-Revised; TR, Total Recall; DR, Delayed Recall; RECOG, Delayed Recognition; TMTA, Trail Making Test Part A; TMTB, Trail Making Test Part B; COWA, Controlled Oral Word Association; IRF, independent review facility.

Fig. 2.

Neurocognitive test scores across time for patients with progression-free survival >6 months. Values represent median test scores of patients in the BEV (upper panel) and BEV + CPT-11 (lower panel) study arms with progression-free survival >6 months, according to IRF review, and completed tests at the indicated time of neurocognitive assessment, standardized using normative data from the general population (i.e., mean = 0, SD = 1). Values under the x-axis represent the number of patients assessed at each corresponding timepoint. BEV, bevacizumab; CPT-11, irinotecan; HVLT-R, Hopkins Verbal Learning Test–Revised; TR, Total Recall; DR, Delayed Recall; RECOG, Delayed Recognition; TMTA, Trail Making Test Part A; TMTB, Trail Making Test Part B; COWA, Controlled Oral Word Association; IRF, independent review facility.