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

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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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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