Searchable abstracts of presentations at key conferences in endocrinology
Endocrine Abstracts (2011) 25 S2.3

SFEBES2011 Symposia Novel pathways and treatments in neuroendocrine tumours (4 abstracts)

Tyrosine kinase inhibitors for neuroendocrine tumours

Juan W Valle


Department of Medical Oncology, The Christie NHS Foundation Trust, Wilmslow Road, Manchester, UK.

Neuroendocrine tumours (NETs) are a heterogeneous, uncommon tumours for whom there have been few practice-changing clinical studies. Sub-groups of patients may be defined by site of origin, histological sub-type, mitotic activity and evidence of disease progression.

Chemotherapy is active in patients with advanced pancreatic NETs; however, benefits are modest and associated with significant (albeit manageable) toxicity. Additional treatment options are sparse. Two recently published studies have challenged our treatment paradigm in such patients.

Pancreatic NETs are known to be vascular tumours with over-expression of vascular endothelial growth factor (VEGF, a key regulator in angiogenesis) and VEGF receptor (VEGFR)-2, VEGFR-3, platelet derived growth factor receptors-α and -β and c-kit. Continuous dosing of sunitinib, an oral multi-targeted tyrosine kinase inhibitor of this pathway, has been shown in a phase III, placebo-controlled study to significantly improve the progression-free survival (PFS, the primary end-point), objective response rate and overall survival in patients with well-differentiated, progressive pancreatic NETs1 with acceptable toxicity.

Another pathway over-stimulated in pancreatic NETs is the mammalian target of rapamycin (mTOR); stimulation of this serine-threonine kinase results in angiogenesis, cell growth and proliferation. Everolimus, an inhibitor of mTOR, has recently been shown to significantly prolong PFS in a placebo-controlled, phase III study in patients with progressive low- or intermediate-grade advanced pancreatic NET, once again with manageable toxicity2.

These agents appear to be effective even when other treatments have failed and herald a new era in the management of patients with pancreatic NETs. Emerging evidence suggests that tyrosine kinase inhibitors may also be active in non-pancreatic NETs although mature data is awaited.

Achieving an understanding of the how these agents fit into the treatment algorithm in relation to each other and alongside other treatment modalities as well in early-stage disease will necessitate numerous clinical studies and require significant collaboration amongst investigators.

1. Raymond et al., NEJM 2011 364(6) 501–513.

2. Yao et al., NEJM 2011 364(6) 514–523.

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