“Patients who are diagnosed with advanced breast cancer and start their first-line treatment already show cognitive impairments due to their previous treatments. And luckily, our results show that during first-line treatment for advanced breast cancer with endocrine therapy, with or without a CDK4/6 inhibitor, further cognitive decline is minimal,” lead investigator Maryse Luijendijk, said during her presentation at the annual meeting of the American Society of Clinical Oncology (ASCO).
“It is well known that cancer patients can experience cognitive problems, such as memory loss, problems with concentration or with planning, during or following their treatment,” explained Ms. Luijendijk, a PhD candidate in the department of Psychosocial Research and Epidemiology at the Netherlands Cancer Institute, in Amsterdam. “Much is known about the effects of chemotherapy or irradiation to the brain, but evidence into endocrine therapy is scarce, which is surprising because cognitive effects are biologically plausible.
“We know that estrogen plays an important role in neuronal functioning and that certain types of endocrine therapies are able to cross the blood-brain barrier, where they may interact with estrogen receptors distributed widely throughout the brain … We know that CDK4/6 inhibitors may either negatively affect cognitive function by increased fatigue due to cytokine release or by interrupting the cell cycle of healthy cells, or positively, as they have been associated with reduced inflammation and remyelination.”
Initial results of the SONIA trial, reported at ASCO last year, examined overall and progression-free survival in patients with HR-positive, HER2-negative metastatic breast cancer and no prior treatment for advanced disease. Findings for those who were randomized to treatment with nonsteroidal aromatase inhibition either with or without the addition of CDK4/6 inhibitors showed no between-group differences, explained Ms. Luijendijk.
The new results, described as being from the SONIA-EfFECT (Evaluation of cognitive functioning in patients with metastatic breast cancer treated with endocrine or combined therapy) trial, were based on the authors investigating cognitive functioning in the same cohort used in the SONIA trial plus a control group.
In SONIA-EfFECT, patients who participated in SONIA were asked to identify a female relative or friend without cancer to serve as a cancer-free control. Members of the 130-patient control group were matched for age, education, and computer use.
Participants in the SONIA trial and control group were asked to complete the Amsterdam Cognition Scan, an online neuropsychological test battery at baseline and again after 9 months of treatment. Of those patients from SONIA, 130 had received first-line treatment with aromatase inhibitors with CDK4/6 inhibition (Arm A) and 130 had received aromatase inhibitors without CDK4/6 inhibition (Arm B).
Baseline assessments for SONIA-EfFECT were completed for 260 patients from SONIA and the full 130-person control group. Follow-up assessments were completed for 119 members of the control group and 199 patients from the original SONIA trial (108 from Arm A, and 91 from Arm B). Patients from SONIA who switched to second-line treatment within 9 months were not retested.
Patients in both SONIA arms performed significantly worse than the controls on the domains of verbal memory, working memory, processing speed, executive function, and motor function. In both patient arms and the controls, standardized regression-based change scores showed limited decline in cognitive function over the 9-month interval. Minimal differences in cognitive change were observed between the patients treated with and without CDK4/6 inhibitors, and between patients and the controls, according to the abstract for SONIA-EfFECT, published in the program for the annual meeting of ASCO.
“At baseline, patients show worse cognitive function across all domains compared to the controls. And as expected, there were no differences between the two treatment arms,” Ms. Luijendijk explained. After 9 months of treatment, the testing showed limited further decline among patients, “and even some improvement on some tests,” with minimal differences between treatment arms “implying that cognitive function does not need to be an aspect when deciding on treatment.”
Ms. Luijendijk reported no relevant disclosures.