Real-World Effectiveness of Capecitabine and Temozolomide Across Endocrine and Neuroendocrine Neoplasm Subtypes (ENENs): A Population-Based Cohort Study from Alberta, Canada (2011-2021).

Capecitabine plus temozolomide (CAPTEM) improves progression-free survival (PFS) in pancreatic endocrine and neuroendocrine neoplasms (PNENs), yet its real-world effectiveness across other endocrine and neuroendocrine neoplasm (ENEN) subtypes remains uncertain. We conducted a retrospective population-based cohort study including 159 adults with ENENs treated with CAPTEM in Alberta, Canada (2011-2021). Patients were stratified by primary tumor site, treatment line, and number of CAPTEM cycles received. Kaplan-Meier methods and Cox proportional hazards models adjusted for age and sex were used to evaluate PFS and overall survival (OS). Compared with pancreatic neuroendocrine neoplasms PNENs, gastrointestinal neuroendocrine neoplasms (GINENs) demonstrated similar PFS and OS. In contrast, pulmonary neuroendocrine neoplasms (PuNENs) and other ENENs (OENENs) were associated with significantly shorter PFS and OS. Use of CAPTEM in the first-line setting was associated with improved PFS (HR 0.56, 95% CI 0.40-0.78, p < 0.001) and OS (HR 0.42, 95% CI 0.29-0.62, p < 0.001). Receipt of ≥6 treatment cycles was also strongly associated with superior PFS (HR 0.22, 95% CI 0.16-0.32, p < 0.001) and OS (HR 0.22, 95% CI 0.14-0.34, p < 0.001). CAPTEM shows comparable real-world effectiveness in GINENs and PNENs but appears less effective in PuNENs and other OENEN subtypes. Early initiation and adequate treatment duration are key factors associated with improved survival outcomes.