Donepezil for the Treatment of Cognitive Impairment in Breast Cancer Survivors After Adjuvant Chemotherapy

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In the phase III WF-97116 trial reported in the Journal of Clinical Oncology, Rapp et al found that treatment with the cognitive enhancer donepezil did not improve memory or other cognitive functions vs placebo in breast cancer survivors with cancer-related cognitive impairment 1 to 5 years after adjuvant chemotherapy.

Study Details

In the trial, 276 breast cancer survivors who had received at least four cycles of adjuvant chemotherapy and reported cognitive impairment and memory problems at 1 to 5 years after chemotherapy were enrolled from multiple Wake Forest National Cancer Institute Community Oncology Research Program (NCORP) sites between July 2017 and July 2021. Patients were randomly assigned to receive donepezil at 5 mg once daily for 6 weeks titrated to 10 mg once daily for 18 weeks (n = 140) or placebo (n = 136). Cognitive functioning using various instruments was assessed at baseline and at 12, 24 (end of intervention), and 36 weeks. The primary outcome measure was memory at week 24, assessed using the Hopkins Verbal Learning Test-Revised (HVLT-R; score range = 0–6, higher being better).

Key Findings

Random assignment occurred at a mean of 29.6 ± 14.2 months after chemotherapy.

At 24 weeks, there was no significant difference in least-squares mean HVLT-R scores between the donepezil group and the placebo group (25.98 vs 26.50, P = .32). At 12 and 36 weeks, scores were 24.4 vs 24.5 and 25.1 vs 25.9, respectively.

No significant differences between the donepezil group and the placebo group were observed at 12, 24, or 36 weeks for the secondary outcome measures of attention, executive function, verbal fluency, processing speed, or self-reported cognitive functioning. Outcomes were not affected by receipt of endocrine therapy or menopausal status.

The investigators concluded, “Breast cancer survivors 1 [to] 5 years after completing chemotherapy with documented memory problems randomly assigned to 24 weeks of 5 [to] 10 mg of donepezil once daily did not perform differently at the end of treatment on tests of memory, other cognitive functions, or subjective functioning than those randomly assigned to placebo.”

Stephen R. Rapp, PhD, of the Department of Psychiatry and Behavioral Medicine, Wake Forest University School of Medicine, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: The study was supported by a grant from the National Cancer Institute. For full disclosures of the study authors, visit

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.