Effect of Donepezil on Dimensions of Patient-Reported Cognitive Impairment in Breast Cancer Survivors: Secondary Analysis of the NCORP REMEMBER Trial (WF-97116).

Abstract

Cancer-related cognitive impairment (CRCI) is a prevalent and persistent problem among many breast cancer survivors (BCS). Results from the randomized, placebo-controlled REMEMBER clinical trial (WF-97116) showed no improvement in cognitive test performance among BCS 1-5 years after chemotherapy after 24 weeks of daily donepezil compared with placebo. Here we present results for an important secondary outcome, patient-reported cognitive impairment, and explore the correlates of CRCI. Women age ≥18 years with a history of breast cancer who completed ≥4 cycles of adjuvant cytotoxic chemotherapy 1-5 years before enrollment and self-reported CRCI were eligible. We enrolled participants through the Wake Forest National Cancer Institute Community Oncology Research Program (NCORP) Research Base and randomly assigned participants to a 24-week course of once daily donepezil (single 5 mg dose titrated to 10 mg after 6 weeks) or placebo. We administered the Functional Assessment of Cancer Therapy-Cognitive Function (FACT-Cog), a patient-reported outcome measure, at baseline and weeks 12, 24 (end of intervention), and 36 (wash-out). Mixed-effects repeated-measures analysis of covariance models assessed treatment differences in four FACT-Cog subscales. Additionally, demographic, clinical, and cognitive performance correlates of CRCI severity at baseline were examined. A total of 276 patients (mean age, 57.1; standard deviation, 10.5) from 87 NCORP sites were randomly assigned to donepezil (n = 140) or placebo (n = 136). There were no statistically significant treatment differences on the four CRCI outcomes: perceived cognitive impairments, cognitive abilities, impact on quality of life, and observations by others at 24 weeks. CRCI severity at baseline was associated with demographic variables, cognitive performance, and comorbidities, but not cancer-related variables. There were no discernible reductions in patient-reported CRCI attributable to donepezil, consistent with results for cognitive performance. CRCI severity appears to be multidimensional in nature, suggesting multifactorial prevention and treatment approaches might be beneficial.