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

Sam Lubner*, Yang Feng, Mary Mulcahy, Peter O'Dwyer, Guang Yu Giang, J. Louis Hinshaw, Dustin Deming, Leonard Klein, Ursina Teitelbaum, Jennifer Payne, Paul Engstrom, Philip Stella, Neal Meropol, Al Benson

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

2 Scopus citations


Lessons Learned: 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. Background: 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). Methods: 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 acting-repeatable (LAR) for patients who had been on a stable dose. The primary objective was to determine the 4-month progression-free survival (PFS). Results: Forty-four patients were evaluated per protocol. The 4-month PFS was 78.5%. The partial response rate was 13.6% (6/44), stable disease was 54.5% (24/44), 9.1% (4/44) had progressive disease, and 10/44 were not evaluable for response. Common toxicities included fatigue, hypertension, nausea, and headache, and most were grade 1–2. Median PFS was 8.7 months, and overall survival was 27.5 months. Conclusion: Motesanib (AMG 706) demonstrated a 4-month PFS that met the per-protocol definition of efficacy. Fatigue and hypertension were the most common toxicities, and few grade 3–4 toxicities were encountered. The progression-free survival of 8.7 months in all NETs merits further study.

Original languageEnglish (US)
Pages (from-to)1006-e104
Issue number9
StatePublished - Sep 2018

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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