Cognitive function in patients with HR+ advanced breast cancer treated with endocrine therapy with or without CDK4/6 inhibitors in the SONIA trial.
Authors: Luijendijk Maryse , Lee Meeuw Kjoe Philippe , Wortelboer Noor , Van Ommen - Nijhof Annemiek , Agelink van Rentergem Joost , Vermeulen Ivar , Konings Inge , Jager Agnes , Sonke Gabe S. , Van Der Wall Elsken , Schagen Sanne B. 
Published: June 2024

1016 Background: Given the important role of estrogen in normal neuronal function, endocrine treatment for breast cancer may adversely affect cognition, including memory, planning and attention. Previous studies showed mixed results but were often underpowered. It is unknown whether CDK4/6 inhibitors have cognitive side effects. SONIA-EfFECT is a side-study of the SONIA trial that investigates cognitive functioning in HR+ advanced breast cancer patients treated with endocrine therapy with or without CDK4/6 inhibitors. Methods: Patients randomized in the SONIA trial to receive first-line treatment with aromatase inhibitors with (Arm A) or without (Arm B) CDK4/6 inhibition were approached to participate in the SONIA-EfFECT side-study. Patients were asked to identify a female relative or friend without cancer to serve as a cancer-free control. Both patients and controls were asked to complete the Amsterdam Cognition Scan, an online neuropsychological test battery, at baseline and after 9 months. Patients who switched to second-line treatment within nine months were not retested. To prevent confounding effects of imbalance in age, education, and computer use between patient groups and controls, propensity score matching was performed. Baseline cognitive function was assessed by converting raw test scores to standardized Z-scores adjusted for computer use, based on baseline performance in the matched control group. To investigate the effect of endocrine therapy ±CDK4/6 inhibitors over time, standardized regression-based change scores were computed based on baseline and follow-up performance in the matched control group. One-way analyses of variance were conducted to compare baseline performance and cognitive change between the two arms and the matched control group. Results: 260 patients (130 Arm A/130 Arm B) and 196 controls completed baseline assessments. A matched sample of 130 controls was selected. 199 patients (108 Arm A/91 Arm B) and 119 matched controls had complete follow-up assessments. Patients in both study 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. Moreover, minimal differences in cognitive change were observed between the patients treated with and without CDK4/6 inhibitors, and between patients and the controls. Conclusions: HR+ advanced breast cancer patients show worse cognitive function on all cognitive domains compared to a control group without cancer. Nine months of treatment with endocrine therapy with or without CDK4/6 inhibitors does not further worsen cognitive function in this study. Clinical trial information: NCT03425838 .