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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 everolimus and factors influencing the PFS and OS. Results One hundred patients were evaluated. The PFS associated with the G1/G2 types tended to be significantly longer than that associated with the G3/NEC types (hazard ratio [HR], 0.45; p =0.005). A multivariate 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 presence of treatment with metformin (yes; HR, 0.29; p =0.044). The median OS was 63.8 months. In the multivariate 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). Conclusions 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.