Everolimus in the Treatment of Neuroendocrine Tumors of the Respiratory and Gastroenteropancreatic Systems

Flaum, Nicola; Valle, Juan W.; Mansoor, Wasat; McNamara, Mairéad G.

doi:10.2217/fon.16.23

Cited by 3 publications

(2 citation statements)

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“…A major issue with carcinoid tumors is the rarity of the disease and therefore it is difficult to conduct such studies. Also, there is an issue if drugs such as; everolimus could be administered as adjuvant therapy and for how long after surgery 52. Everolimus could be used as treatment in the case that surgery is not possible, or could be used as adjuvant therapy in the case that surgery is not possible and only endoscopic debulking procedures are possible.…”

Section: Discussionmentioning

confidence: 99%

Massive parallel sequencing and digital gene expression analysis reveals potential mechanisms to overcome therapy resistance in pulmonary neuroendocrine tumors

Walter¹,

Vollbrecht²,

Christoph³

et al. 2016

J. Cancer

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Background: Lung cancer is the leading cause of cancer-related deaths worldwide. 25% show neuroendocrine differentiation (typical/atypical carcinoids, large-/small-cell neuroendocrine carcinomas). Carcinoids present with long survival rates, but metastatic carcinoids correlate with decreased survival and are commonly insensitive to standard chemotherapy or radiation. Therefore, novel therapeutic strategies are urgently needed.Material and methods: 70 representative tumor specimens were used for next-generation sequencing analysis of 14 genes related to therapy response. Additionally, mRNA-expression profiles of 60 matching samples were determined for 13 selected drug targets by using the NanoString nCounter technology.Results: A number of features known to sensitize tumors for different targeted therapies could be identified, which hopefully improve the clinical management of this subgroup of lung neoplasias. In particular, EGFR expression was observed in the investigated tumors in a noteworthy manner. Additionally, MDM2 was strongly expressed in the majority of all samples whereas the expression of its physiological inhibitor, CDKN2A, was nearly absent in all low-grade tumors. TP53 showed a high frequency of variants in high-grade tumors but mutations were rare in carcinoids.Conclusion: Based on our results, therapeutic approaches with MDM2-inhibitors and monoclonal anti-EGFR antibodies may be promising in pulmonary carcinoid tumors.

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Section: Discussionmentioning

confidence: 99%

Massive parallel sequencing and digital gene expression analysis reveals potential mechanisms to overcome therapy resistance in pulmonary neuroendocrine tumors

Walter¹,

Vollbrecht²,

Christoph³

et al. 2016

J. Cancer

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“…Everolimus [Afinitor ® , RAD-001 (40- O -(2-hydroxyethyl)-rapamycin)] is a rapamycin analog (rapalog) that has been developed to improve the pharmacokinetic characteristics of rapamycin, mostly its oral bioavailability 28–30…”

Section: Overview Of Pharmacology Mode Of Action Pharmacokinetics Omentioning

confidence: 99%

Emerging use of everolimus in the treatment of neuroendocrine tumors

Gajate¹,

Martínez-Sáez²,

Alonso‐Gordoa³

et al. 2017

CMAR

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Neuroendocrine tumors (NETs) consist of a diverse family of malignancies, which are derived from neuroendocrine cells, most commonly originating from the gastroenteropancreatic (GEP) tract or the bronchopulmonary system. In general, NETs are more indolent than epithelial tumors, with median survival rates of longer than 30 months. The upregulation of mTOR pathway has been shown to play a pivotal role in NET pathogenesis. Inhibition of mTOR protein with everolimus represents a progress in the treatment of advanced NETs. Everolimus has shown a significant improvement in progression-free survival (PFS) among patients with pancreatic NETs (pNETs) and nonfunctional GEP and lung NETs in the Phase III RAD001 in Advanced Neuroendocrine Tumors (RADIANT)-3 and RADIANT-4 studies, respectively. In addition, the combination of everolimus with octreotide showed a clinically significant improvement versus octreotide alone in functional NETs in the RADIANT-2 trial. These studies led to the US Food and Drug Administration (FDA) and European Medical Agency (EMA) approval of everolimus. Safety profile of everolimus is generally acceptable. The most common adverse events are stomatitis, diarrhea, rash and fatigue. There is a growing range of novel treatment options in the setting of NETs, but there are no data comparing the activity of different treatment strategies. Thus, treatment decisions are based on different aspects, such as clinical course, patient symptomatology, primary tumor site, tumor functionality, rate of progression and burden of disease. Further research is required to clarify the treatment sequencing to achieve the maximum prolongation in survival and maintenance of quality of life. Future research should concentrate on identification of predictive biomarkers for benefit from different therapies, and studies should also include quality of life as an important measurement in this disease.

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Unravelling the pharmacologic opportunities and future directions for targeted therapies in gastro-intestinal cancers part 2: Neuroendocrine tumours, hepatocellular carcinoma, and gastro-intestinal stromal tumours

Neuzillet

Mestier²,

Rousseau³

et al. 2018

Pharmacology & Therapeutics

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Everolimus in the Treatment of Neuroendocrine Tumors of the Respiratory and Gastroenteropancreatic Systems

Cited by 3 publications

References 72 publications

Massive parallel sequencing and digital gene expression analysis reveals potential mechanisms to overcome therapy resistance in pulmonary neuroendocrine tumors

Massive parallel sequencing and digital gene expression analysis reveals potential mechanisms to overcome therapy resistance in pulmonary neuroendocrine tumors

Emerging use of everolimus in the treatment of neuroendocrine tumors

Unravelling the pharmacologic opportunities and future directions for targeted therapies in gastro-intestinal cancers part 2: Neuroendocrine tumours, hepatocellular carcinoma, and gastro-intestinal stromal tumours

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