Cognitive impairment during anti-EGFR targeted therapy in metastatic colorectal cancer patients.

Abstract

12085 Background: Cognitive function is a critical determinant of psychosocial adaptation and quality of life in patients with cancer. Even mild cognitive impairment may negatively affect daily functioning, communication, compliance, and social participation. The psychosocial consequences of cognitive changes during medical treatment are insufficiently studied in metastatic colorectal cancer (mCRC) patients. Anti-EGFR-targeted therapy affects downstream MAPK signaling, a pathway involved in synaptic plasticity and cognitive processes. This provides a biological rationale for investigating cognitive outcomes and their psychosocial relevance. Methods: This study included patients with mCRC who received FOLFOX6-based first-line treatment. The main group (n = 50) received FOLFOX6 combined with an anti-EGFR monoclonal antibody (cetuximab or panitumumab), while the control group (n = 50) received FOLFOX6 +/-bevacizumab. Cognitive function was assessed at baseline and after eight cycles of therapy using the Addenbrooke’s Cognitive Examination–Revised (ACE-R) and the Frontal Assessment Battery (FAB). Changes in cognitive performance were analyzed in relation to patients’ functional vulnerability during ongoing treatment. Cognitive side effects were also evaluated according to CTCAE V.5.0. Results: Baseline cognitive performance was comparable between groups. After eight cycles of therapy, patients receiving anti-EGFR-targeted treatment demonstrated a significant decline in cognitive performance, including ACE-R total scores (from 93 [90; 94.5] to 87 [85; 90.5], p < 0.001), memory domain scores (from 22 [22; 23.5] to 20 [19; 20], p < 0.001), and attention/orientation scores (from 18 [16; 18] to 17 [15; 18], p = 0.005). In contrast, cognitive measures in the control group showed only minimal changes or remained stable over the same observation period. Evaluation according to CTCAE V.5.0. showed cognitive disturbance, memory and concentration impairments of mild and moderate grades, which were significantly more frequent in the anti-EGFR targeted group than in the control group (p<0,005). Conclusions: Anti-EGFR-targeted therapy in metastatic colorectal cancer patients may cause significant cognitive impairment, which undoubtedly contributes to psychosocial maladaptation and reduced quality of life. This pattern of selective cognitive decline may compromise functional independence, communication, and psychosocial adaptation during active anticancer treatment. Routine cognitive assessment during treatment may facilitate early identification of patients at risk and support multidisciplinary management strategies. In addition, the role of the MAPK signaling pathway in memory formation should be studied.