Effectiveness and Prognostic Factors of Everolimus in Patients with Pancreatic Neuroendocrine Neoplasms

Objective The effectiveness of everolimus for the management of pancreatic neuroendocrine neoplasms (PNENs), including the G3/NEC types, remains unclear. We therefore investigated the effectiveness of the drug for the management of PNENs.Methods We analyzed the progression-free survival (PFS) and overall survival (OS) associated with ever-olimus and factors influencing the PFS and OS.Results One hundred patients were evaluated. The PFS associated with the G1/G2 types tended to be sig-nificantly longer than that associated with the G3/NEC types [hazard ratio (HR), 0.45; p=0.005]. A multivari-ate analysis showed that the significant factors influencing the PFS were age (<65 years old; HR, 0.44; p= 0.002), grade (G1/G2; HR, 0.42; p=0.006), everolimus treatment line (<= 2nd; HR, 0.55; p=0.031), and pres-ence of treatment with metformin (yes; HR, 0.29; p=0.044). The median OS was 63.8 months. In the multi-variate analysis, the significant factors influencing the OS were grade (G1/G2; HR, 0.21; p<0.001), volume of liver metastasis (<= 25%; HR, 0.27; p<0.001), everolimus treatment line (<= 2nd; HR, 0.27; p<0.001), and presence of primary tumor resection (yes; HR, 0.33; p=0.005).Conclusion The effectiveness of everolimus in the management of G3/NEC types and prognoses tended to be poorer than those associated with the G1/G2 types. Everolimus combined with metformin and early-line treatment with everolimus may be effective for managing advanced PNENs.