Abstract OT1-04-06: Evaluation of cognitive functioning in patients with metastatic breast cancer treated with endocrine or combined therapy
Authors: Kjoe Philippe Lee Meeuw , van der Wall Elsken , Konings Inge , Jager Agnes , Sonke Gabe , van Ommen-Nijhof Annemiek , Schagen Sanne 
Published: March 2020

Abstract
Background: A subset of patients with breast cancer is vulnerable to treatment-related cognitive problems. However, relatively little is known about the cognitive effects of endocrine treatment and the novel cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitors in the metastatic setting. Research on possible cognitive effects of these therapies is needed, since cognitive impairment can affect role functioning, independence and quality of life.
Trial design: The current study is a side study of the SONIA (Selecting the optimal position of CDK4/6 inhibitors in hormone-receptor-positive advanced breast cancer) trial: a multicenter, randomized phase III study. The side study is an observational study with nine months of follow-up, comparing two intervention groups (first line non-steroidal aromatase inhibitor + CDK4/6 inhibition vs. single agent non-steroidal aromatase inhibitor) and a reference group of people without a history of cancer. Cognition will be measured at start of treatment (T0) and nine months later (T1), using the Amsterdam Cognition Scan, a validated online neuropsychological test battery that is completed at home without supervision. It includes tests of among others attention, memory, and executive functioning, and two questionnaires on anxiety and depression, and fatigue.
Specific aims: The main objective is to evaluate if there is a difference in cognitive functioning over time in patients with metastatic breast cancer who will undergo first line endocrine treatment + CDK4/6 inhibition vs. endocrine treatment alone.
Eligibility criteria: All patients who participate in the main SONIA study will be eligible for participation: adult women (≥ 18 years of age) with proven diagnosis of hormone receptor-positive, human epidermal growth factor receptor 2 negative adenocarcinoma of the breast with evidence of loco-regional recurrent or metastatic disease not amenable to resection or radiation therapy with curative intent, for whom chemotherapy is not clinically indicated and who have not received any prior systemic anti-cancer therapy for metastatic disease. Participants in the reference group are patients’ female relatives/friends without a history of cancer and without neurological/psychiatric symptoms influencing cognition, who have a sufficient level of Dutch and access to a computer with internet.
Statistical methods: We will use a mixed effects modeling approach to examine changes in cognition from baseline to follow-up between the two intervention groups and the reference group, adjusting for non-ignorable drop-out patterns. The primary endpoint will be the change from baseline to follow-up on the total score of cognition.
Present accrual and target accrual: With an accrual period of 21 months and 9 months of follow-up, inclusion of 260 patients is required. In addition, our already existing reference group (n=157) will be expanded by recruiting participants’ female relatives/friends without a history of cancer.
As of June 2019, 435 patients have enrolled in the main SONIA study. Target accrual is 1050 patients.
Contact information
Study coordinator: Philippe Lee Meeuw Kjoe, Netherlands Cancer Institute, p.lee.meeuw.kjoe@nki.nl
PI: Elsken van der Wall, MD, PhD, UMC Utrecht Cancer Center, E.vanderWall@umcutrecht.nl
PI: Sanne Schagen, PhD, Netherlands Cancer Institute, s.schagen@nki.nl
Citation Format: Philippe Lee Meeuw Kjoe, Elsken van der Wall, Inge Konings, Agnes Jager, Gabe Sonke, Annemiek van Ommen-Nijhof, Sanne Schagen. Evaluation of cognitive functioning in patients with metastatic breast cancer treated with endocrine or combined therapy [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr OT1-04-06.