It seems donepezil did not show any cognitive benefit when added to standard adjuvant chemotherapy for breast cancer. Unfortunately, adequate treatment for ‘chemo-brain’ remains elusive. There is data that a lipid structure, S1P, may be linked to this process and may be ‘druggable’ with some of the MS agents.
To test efficacy of donepezil, a cognitive enhancer, to improve memory in breast cancer survivors who report cancer-related cognitive impairment 1-5 years postchemotherapy.
Adult female BCS exposed to ≥4 cycles of adjuvant chemotherapy 1-5 years before enrollment who reported cancer-related cognitive impairment were eligible. Participants, enrolled at sites affiliated with the Wake Forest NCI Community Oncology Research Program (NCORP) Research Base, were randomly assigned to receive 5 mg of donepezil once daily for 6 weeks titrated to 10 mg once daily for 18 weeks or placebo. Cognition and self-report cognitive functioning was assessed at baseline, 12, 24 (end of intervention), and 36 (washout) weeks postrandomization. Mixed-effects repeated measures analysis of covariance models were used to assess treatment differences in immediate recall (primary outcome) on the Hopkins Verbal Learning Test-Revised (HVLT-R) and other cognitive domains (secondary outcomes) with covariates of treatment, time, time by treatment interaction, baseline outcome level, age stratification, and an unstructured covariance matrix to account for within participant correlation over time.
Two hundred seventy-six BCS from 87 NCORP practices (mean age, 57.1, standard deviation [SD], 10.5) who were at a mean of 29.6 months (SD, 14.2) postchemotherapy were randomly assigned to donepezil (n = 140) or placebo (n = 136). At 24 weeks, treatment groups did not differ on HVLT-R scores (donepezil mean = 25.98, placebo = 26.50, P = .32). There were no statistically significant differences between treatments at 12, 24, or 36 weeks for attention, executive function, verbal fluency, processing speed, or self-reported cognitive functioning. Endocrine therapy and menopausal status did not affect results.
BCS 1-5 years after completing chemotherapy with documented memory problems, randomly assigned to 24 weeks of 5-10 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.
MammaPrint did not predict distant recurrence, but it did predict patients who may benefit from extended hormonal therapy. We do have breast index, so now we have options. Breast index can predict the possibility of recurrence though by helping to determine the level of risk.
Adding Inavolisib to CKD4/6 inhibitor and AI improved progression-free survival (almost doubled 15 vs 7m) but toxicity was higher still in the single digits (hyperglycemia, diarrhea, stomatitis… all less than 6% G3/4).
Well done study showing a 20% decrease in recurrence risk when using dose dense therapy [EC]/D compared to conventional dose [FEC]/D. Sometimes it is worth it to push.
Myth busted. In aggressive breast cancer, no need to start chemotherapy now, ET and CKD4/6 inhibitors are better tolerated with significant progression-free survival (PFS) benefit and same response rate.
Datopotamab Deruxtecan is a new ADC that will likely be approved in the near future. The payload is the same as used in Enhertu, but the antibody is directed at TROP2. This report is from the TROPION-pan tumor study and shows a promising ORR in HR+/HER2- MBC. There is reasonable data for this compound in 2L met-NSCLC in the TROPION-LUNG01 study with an improvement in PFS compared to docetaxel of 4.4 vs 3.7 months. Dato also is effective in patients with actionable genetic alterations in the 2L setting. There is also an ongoing study on its use in the 1L setting for met-NSCLC in combination with pembrolizumab and chemotherapy.
FCS Hematology Oncology Review creates a platform for our physician network to observe the most recent articles and studies available in the oncology and hematology world. By sharing these articles we are building our wealth of knowledge of new observations and treatments as they come available.
