E4206: AMG 706 and Octreotide in Patients with Low-Grade Neuroendocrine Tumors.

The Oncologist
Sam J LubnerAl Benson

Abstract

Rate of progression-free survival at a particular point in time, i.e., a landmark analysis, is a difficult endpoint for a heterogenous malignancy such as neuroendocrine cancer.Landmark analyses can also be complicated by evolution in the standard of care during the conduct of a clinical trial.Improvements in biomarker development would be useful in developing future clinical trials in NET to better tailor individualized therapies and assess for possible efficacy endpoints. Neuroendocrine tumors (NETs) are rare malignancies of the gastrointestinal (GI) tract that are highly vascularized and overexpress vascular-endothelial growth factor (VEGF). Sunitinib has demonstrated efficacy in the pancreatic subset of NET. This study explored the activity of another oral VEGF inhibitor, AMG 706 or motesanib, a multikinase inhibitor that targets receptor tyrosine kinases, including VEGFR1, VEGFR2, VEGFR3, KIT, RET, and PDGFR (IC50s = 2, 3, 6, 8, 59, and 84 nM, respectively). This was a single-arm, first-line, phase II study run through the Eastern Cooperative Oncology Group. Patients with low-grade NET (as defined by central confirmation of Ki-67 of 0%-2%) were administered a flat dose of 125 mg per day orally combined with octreotide long ...Continue Reading

References

Mar 8, 2008·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·James C YaoJaffer A Ajani
Jul 10, 2008·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Matthew H KulkeCharles S Fuchs
Feb 11, 2011·The New England Journal of Medicine·Eric RaymondPhilippe Ruszniewski
Feb 11, 2011·The New England Journal of Medicine·James C YaoUNKNOWN RAD001 in Advanced Neuroendocrine Tumors, Third Trial (RADIANT-3) Study Group
Dec 26, 2015·Lancet·James C YaoUNKNOWN RAD001 in Advanced Neuroendocrine Tumours, Fourth Trial (RADIANT-4) Study Group

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Citations

Mar 15, 2019·Journal of Hematology & Oncology·Shuang QinKongming Wu

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