Pancreatic neuroendocrine tumors (PanNETs) are rare neoplasms with a more favorable prognosis than pancreatic adenocarcinoma. However, up to 60% of patients with PanNETs present with advanced disease or will recur after surgical resection, requiring multimodal therapy to improve clinical outcomes. In 2011, two phase 3, randomized, placebo-controlled trials provided optimism regarding the treatment of malignant PanNETs. The tyrosine kinase inhibitor sunitinib and the mTOR inhibitor everolimus were effective in improving progression-free survival in advanced PanNETs. These two trials involved patients with well-differentiated or intermediate/low-grade PanNETs as defined by previous histological classifications including the World Health Organization (WHO) 2000 system. Patients with poorly differentiated endocrine carcinomas (PDECs) were excluded from these trials, as PDECs are highly malignant tumors commonly treated with cisplatin and etoposide.
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