Cognitive function during endocrine treatment with or without cyclin-dependent kinase 4/6 inhibitors for advanced breast cancer

Background: 

Endocrine treatment for breast cancer may adversely affect cognition. Given the widespread use of cyclin-dependent kinase 4/6 inhibitors (CDK4/6i), assessing the cognitive effects of this combination is important.

Methods: 

In the SONIA trial, patients with hormone receptor–positive, HER2-negative (HR⁺HER2⁻) advanced breast cancer (ABC) starting first-line treatment with an aromatase inhibitor were randomized to treatment with (arm A) or without (arm B) CDK4/6i. Cognitive function was assessed at baseline and after 9 months with the online Amsterdam Cognition Scan. Standardized z scores at baseline and regression-based change scores at 9 months were computed on the basis of matched cancer-free controls. Rates of clinically meaningful decline were compared with estimated false-positive rates of observing decline by chance. 

Results: 

Altogether, 260 patients (arm A, N = 130; arm B, N = 130) and 130 matched controls participated at baseline; 199 patients (arm A, N = 108; arm B, N = 91) and 120 matched controls completed the follow-up. At baseline, patients performed significantly worse than controls across all cognitive domains. Over the course of 9 months, no group-level decline in cognitive function occurred in either treatment arm, with minimal differences between treatment arms. At the individual level, however, the rate of clinically meaningful decline in patients (arm A, 15.7%; arm B, 14.3%) but not in controls (6.7%) was significantly higher than the false-positive rate (7.5%), which indicates decline in a small subset of patients. 

Conclusions: 

Patients with HR⁺HER2⁻ ABC showed impaired cognitive function at initial diagnosis compared to cancer-free controls. During first-line endocrine treatment with aromatase inhibitors, cognitive function declined in a small group of patients, regardless of the addition of CDK4/6i.