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Emerging Treatment Options for Gastroenteropancreatic Neuroendocrine Tumors.

ABSTRACT: Treatment options for neuroendocrine tumors (NETs) and carcinomas (NECs) are expanding. Early-phase studies have shown preliminary evidence of the antitumor activity of alpha-emitting peptide receptor radionuclide therapy (PRRT), and novel radiopeptides incorporating somatostatin receptor antagonists (rather than agonists) have been developed. Several tyrosine kinase inhibitors (TKIs) with antiangiogenic potential have been evaluated in patients with NETs, including lenvatinib, axitinib, cabozantinib and pazopanib. Recently, two phase 3 clinical trials have demonstrated the efficacy and safety of surufatinib, an inhibitor of vascular endothelial growth factor receptor (VEGFR)-1, -2, -3, fibroblast growth factor receptor (FGFR)-1 and colony stimulating factor-1 receptor (CSF-1R), in patients with pancreatic and extra-pancreatic NETs. Multiple clinical trials of combination immunotherapy have been recently completed, but interpretation of the results is hampered by small samples sizes and discordant outcomes. This review summarizes recent data on emerging treatments for neuroendocrine neoplasms.

SUBMITTER: Cives M

PROVIDER: S-EPMC7696369 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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Emerging Treatment Options for Gastroenteropancreatic Neuroendocrine Tumors.

Cives Mauro M Pelle' Eleonora E Strosberg Jonathan J

Journal of clinical medicine 20201113 11

Treatment options for neuroendocrine tumors (NETs) and carcinomas (NECs) are expanding. Early-phase studies have shown preliminary evidence of the antitumor activity of alpha-emitting peptide receptor radionuclide therapy (PRRT), and novel radiopeptides incorporating somatostatin receptor antagonists (rather than agonists) have been developed. Several tyrosine kinase inhibitors (TKIs) with antiangiogenic potential have been evaluated in patients with NETs, including lenvatinib, axitinib, cabozan ...[more]

PMID: 33202931

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Project description:Poorly differentiated gastroenteropancreatic neuroendocrine carcinomas (GEPNECs) are a rare neoplasm with a bleak prognosis. Currently there are little prospective data available for optimal treatment. This review discusses the current available regimens and the future direction for the treatment of GEPNECs. Treatment plans for GEPNECs are often adapted from those devised for small cell lung cancer; however, differences in these malignancies exist, and GEPNECs require their own treatment paradigms. As such, current first-line treatment for GEPNECs is platinum-based chemotherapy with etoposide. Studies show that response rate and overall survival remain comparable between cisplatin and carboplatin versus etoposide and irinotecan; however, prognosis remains poor, and more efficacious therapy is needed to treat this malignancy. Additional first-line and second-line treatment options beyond platinum-based chemotherapy have also been investigated and may offer further treatment options, but again with suboptimal outcomes. Recent U.S. Food and Drug Administration approval of peptide receptor radionuclide therapy in low- and intermediate-grade neuroendocrine tumors may open the door for further research in its usefulness in GEPNECs. Additionally, the availability of checkpoint inhibitors lends promise to the treatment of GEPNECs. This review highlights the lack of large, prospective studies that focus on the treatment of GEPNECs. There is a need for randomized control trials to elucidate optimal treatment regimens specific to this malignancy. IMPLICATIONS FOR PRACTICE: There are limited data available for the treatment of poorly differentiated gastroenteropancreatic neuroendocrine carcinomas (GEPNECs) because of the rarity of this malignancy. Much of the treatment regimens used in practice today come from research in small cell lung cancer. Given the poor prognosis of GEPNECs, it is necessary to have treatment paradigms specific to this malignancy. The aim of this literature review is to summarize the available first- and second-line GEPNEC therapy, outline future treatments, and highlight the vast gap in the literature.

Project description:IntroductionNeuroendocrine neoplasms (NENs) are a rare group of tumors exceptionally heterogeneous, with clinical presentation ranging from well differentiated more indolent tumors to poorly differentiated very aggressive forms. Both are often diagnosed after the metastatic spread and require appropriate medical treatment. A high priority need in the management of this disease is the identification of effective therapeutic strategies for advanced and metastatic patients. The recent TALENT trial demonstrated the efficacy of lenvatinib, a multi-tyrosine kinase inhibitor, in patients with gastroenteropancreatic neuroendocrine tumors (GEP-NETs) with no other treatment indication. Further development of this drug in advanced NETs is warranted.MethodsWe investigated potential clinical and molecular determinants of lenvatinib response in human primary cultures derived from patients with GEP-NET of different grades and sites of origin. We correlated response to treatment with patient clinical characteristics, with the mutational status of 161-cancer associated genes and with the expression levels of MKI-related genes.ResultsLenvatinib exerted a significant antitumor activity in primary GEP-NET cells, with median survival inhibitions similar or higher than those of standard frontline treatments. Of the 11 primary cultures analyzed in our case series, 6 were classified as responder showing a significant survival inhibition, and 5 as non-responder. We observed that the overexpression of HRAS in the original tumor tissue compared to the matched healthy tissue significantly correlated with responsiveness of primary cells to lenvatinib (p=.048). All 5 non-responder cultures showed normal HRAS expression, while of the 6 responder cultures, 4 had HRAS overexpression. Overexpression of HRAS was not associated with gene mutation. None of the other evaluated clinical variables (grade, Ki67, site of origin and syndromic disease) or molecular markers correlated with response.DiscussionLenvatinib appears to be a highly effective drug for the treatment of NETs. The evaluation of HRAS expression in the tumor tissue might improve patient selection and optimize therapeutic outcome.

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Emerging Treatment Options for Gastroenteropancreatic Neuroendocrine Tumors.

Publications

Emerging Treatment Options for Gastroenteropancreatic Neuroendocrine Tumors.

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