Can Donepezil Reduce Late Cancer-Related Cognitive Impairment in Breast Cancer Survivors?

By: Julia Fiederlein Cipriano
Posted: Friday, July 21, 2023

Although previous studies of late cancer-related cognitive impairment have suggested that repurposing cognitive-enhancing medication may benefit breast cancer survivors, according to Steve R. Rapp, PhD, of the Wake Forest University School of Medicine, Winston-Salem, North Carolina, and colleagues, this did not seem to hold true with the acetylcholine esterase inhibitor donepezil versus a placebo in those who underwent prior chemotherapy. The results of the phase III Wake Forest National Cancer Institute Community Oncology Research Program (NCORP) Research Base REMEMBER trial, which were presented during the 2023 American Society for Clinical Oncology (ASCO) Annual Meeting (Abstract 12004), underscore the unmet need for more effective options in this population.

Breast cancer survivors from 87 NCORP sites with evidence of memory deficit and self-reported cancer-related cognitive impairment who completed at least four cycles of chemotherapy between 1 and 5 years prior to enrollment were randomly assigned to receive a 24-week course of donepezil (5 mg daily for 6 weeks titrated to 10 mg daily for 18 weeks; n = 140) or a placebo (n = 136). Based on the results of the Hopkins Verbal Learning Test-Revised, the mean memory score at 24 weeks did not appear to differ between patients treated with donepezil versus the placebo (25.98 vs. 26.50; P = .32). No statistically significant differences in attention, executive function, verbal fluency, or processing speed were observed between the arms at 12, 24, and 36 weeks.

Exploratory analyses adjusting for education, baseline fatigue, and depression, as well as independent analyses accounting for interaction with endocrine therapy and menopausal status, also did not reveal any treatment-related differences for any outcomes. A total of 25 grade 3 or 4 adverse events were reported, with no observable differences in incidence between the arms, according to the investigators.

Disclosure: Dr. Rapp reported no conflicts of interest. For full disclosures of the other study authors, visit coi.asco.org.

2023 ASCO Annual Meeting