The efficacy of everolimus and sunitinib in patients with sporadic or germline mutated metastatic pancreatic neuroendocrine tumors

Journal of Gastrointestinal Oncology
Jose Eduardo NuñezRachel Riechelmann

Abstract

Hyperactivation of mTOR pathway and angiogenesis have been implicated in the pathogenesis of neuroendocrine tumors (NETs). Everolimus, an oral inhibitor of mTOR, and sunitinib, an antiangiogenic drug, are effective targeted therapies approved to treat locally advanced/metastatic pancreatic neuroendocrine tumors (pNETs). Most pNETs are sporadic and mutations in genes involved directly or indirectly in mTOR pathway regulation have been implicated, including somatic mutation in MEN1 in 44% of cases. About 10% of pNETs can be part of hereditary syndromes, e.g., multiple endocrine neoplasia type 1 (MEN1) and Von-Hippel Lindau (VHL), and these patients are underrepresented in pivotal phase III trials. We hypothesized that everolimus would be particularly effective in patients with MEN1-associated pNETs. Likewise, we inferred that sunitinib would also be beneficial to patients with VHL-associated pNETs. We conducted a multicenter retrospective and comparative study to assess the efficacy of everolimus and/or sunitinib in a cohort of patients with advanced pNETs with or without known MEN1 or VHL syndrome. The evaluation of the germline mutational status of VHL and MEN1 genes was retrospectively collected from the medical records. The p...Continue Reading

Citations

Jul 2, 2020·OncoTargets and Therapy·Sven GläskerAlexander O Vortmeyer
May 1, 2020·Current Treatment Options in Oncology·Mark A Lewis
Nov 30, 2020·Endocrine Reviews·Maria Luisa BrandiRajesh V Thakker
May 1, 2021·International Journal of Molecular Sciences·Francesca MariniMaria Luisa Brandi

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