Association between Coexisting Dementia and Mortality in Patients Receiving Oral Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors: A Nationwide Real-world Database Study.

INTRODUCTION

Oral epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are standard first-line treatments for EGFR-mutated non-small cell lung cancer (EGFR-m NSCLC). Because these agents require sustained self-management, cognitive impairment may adversely affect treatment continuity and outcomes. However, the association between coexisting dementia and survival in patients receiving EGFR-TKIs remains unclear.

METHODS

This cohort study used a large Japanese administrative claims database. Patients aged ≥18 years with newly diagnosed NSCLC who initiated first-line EGFR-TKI therapy between 2018 and 2024 were included. Coexisting dementia was identified using diagnosis codes recorded before treatment initiation. The primary outcome was 3-year all-cause mortality. Cox proportional hazards models were used to estimate adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs), adjusting for age, sex, body mass index, smoking status, comorbidity burden, functional status (Barthel Index [BI]), hypertension, dyslipidemia, and calendar year of treatment initiation.

RESULTS

Among 13,281 eligible patients, 282 (2.1%) had coexisting dementia. During follow-up, coexisting dementia was associated with higher all-cause mortality (aHR 1.35, 95% CI 1.06-1.73). In subgroup-specific analyses, preserved functional status (BI = 100) was associated with lower mortality among patients with dementia, whereas multiple clinical factors were associated with mortality among those without dementia.

CONCLUSIONS

Coexisting dementia was associated with poorer survival among patients with EGFR-m NSCLC treated with EGFR-TKIs. Preserved functional status was associated with lower mortality among patients with dementia. These findings suggest that coexisting dementia may identify a clinically vulnerable subgroup in whom functional status warrants careful attention at the initiation of EGFR-TKI treatment.