E4206

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

Sam Lubner*, Yang Feng, Mary Frances 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 B Benson III

*Corresponding author for this work

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

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
JournalOncologist
Volume23
Issue number9
DOIs
StatePublished - Sep 1 2018

Fingerprint

Octreotide
Neuroendocrine Tumors
Disease-Free Survival
Vascular Endothelial Growth Factor A
Fatigue
Clinical Trials
Hypertension
Neoplasms
Receptor Protein-Tyrosine Kinases
Standard of Care
Nausea
Headache
Gastrointestinal Tract
imetelstat
Biomarkers
Survival

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Lubner, Sam ; Feng, Yang ; Mulcahy, Mary Frances ; O'Dwyer, Peter ; Giang, Guang Yu ; Hinshaw, J. Louis ; Deming, Dustin ; Klein, Leonard ; Teitelbaum, Ursina ; Payne, Jennifer ; Engstrom, Paul ; Stella, Philip ; Meropol, Neal ; Benson III, Al B. / E4206 : AMG 706 and Octreotide in Patients with Low-Grade Neuroendocrine Tumors. In: Oncologist. 2018 ; Vol. 23, No. 9. pp. 1006-e104.
@article{e0ad8a3223aa42ea86c36b19ef6e8f63,
title = "E4206: AMG 706 and Octreotide in Patients with Low-Grade Neuroendocrine Tumors",
abstract = "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.",
author = "Sam Lubner and Yang Feng and Mulcahy, {Mary Frances} and Peter O'Dwyer and Giang, {Guang Yu} and Hinshaw, {J. Louis} and Dustin Deming and Leonard Klein and Ursina Teitelbaum and Jennifer Payne and Paul Engstrom and Philip Stella and Neal Meropol and {Benson III}, {Al B}",
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pages = "1006--e104",
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Lubner, S, Feng, Y, Mulcahy, MF, O'Dwyer, P, Giang, GY, Hinshaw, JL, Deming, D, Klein, L, Teitelbaum, U, Payne, J, Engstrom, P, Stella, P, Meropol, N & Benson III, AB 2018, 'E4206: AMG 706 and Octreotide in Patients with Low-Grade Neuroendocrine Tumors', Oncologist, vol. 23, no. 9, pp. 1006-e104. https://doi.org/10.1634/theoncologist.2018-0294

E4206 : AMG 706 and Octreotide in Patients with Low-Grade Neuroendocrine Tumors. / Lubner, Sam; Feng, Yang; Mulcahy, Mary Frances; O'Dwyer, Peter; Giang, Guang Yu; Hinshaw, J. Louis; Deming, Dustin; Klein, Leonard; Teitelbaum, Ursina; Payne, Jennifer; Engstrom, Paul; Stella, Philip; Meropol, Neal; Benson III, Al B.

In: Oncologist, Vol. 23, No. 9, 01.09.2018, p. 1006-e104.

Research output: Contribution to journalArticle

TY - JOUR

T1 - E4206

T2 - AMG 706 and Octreotide in Patients with Low-Grade Neuroendocrine Tumors

AU - Lubner, Sam

AU - Feng, Yang

AU - Mulcahy, Mary Frances

AU - O'Dwyer, Peter

AU - Giang, Guang Yu

AU - Hinshaw, J. Louis

AU - Deming, Dustin

AU - Klein, Leonard

AU - Teitelbaum, Ursina

AU - Payne, Jennifer

AU - Engstrom, Paul

AU - Stella, Philip

AU - Meropol, Neal

AU - Benson III, Al B

PY - 2018/9/1

Y1 - 2018/9/1

N2 - 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.

AB - 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.

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