443P - Prognostic impact of the cumulative dose and dose intensity of everolimus in patients with pancreatic neuroendocrine tumors (PNETs)

Abstract

Pancreatic neuroendocrine tumors (PNETs) are still considered a rare disease, which accounts for approximately 10% of all cases of pancreatic cancer. The oral mTOR inhibitor everolimus has become an established recommended standard therapy for patients with advanced PNETs. Aim of the study is to assess if cumulative dose (CD) and dose intensity (DI) of everolimus may affect survival of advanced PNETs patients. One hundred and sixteen patients (62 males and 54 females, median age 55 years) with advanced PNETs were treated with everolimus for ≥ 3 months. According to a ROC analysis, patients were stratified into two groups, with CD ≤ 3000 mg (Group A; n = 68) and CD > 3000 mg (Group B; n = 48). The response rate and toxicity were comparable in the two groups. However, patients in group A experienced more dose modifications than patients in group B. Median OS was 24 months in Group A whilst in Group B it was not reached (HR: 26.9; 95% CI: 11.0-76.7; p < 0.0001). Patients who maintained a DI higher than 9 mg/day experienced a significantly longer OS and experienced a trend to higher response rate. Overall, our study results showed that both CD and DI of everolimus play a prognostic role for patients with advanced PNETs treated with everolimus. This should prompt efforts to continue everolimus administration in responsive patients up to at least 3000 mg despite delays or temporary interruptions.