E4206: AMG 706 and Octreotide in Patients with Low-Grade Neuroendocrine Tumors
Year: 2018
Type: article
Study design: Clinical Trial
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.
Source: The Oncologist
Institutions: University of Wisconsin–Madison, University of Wisconsin Carbone Cancer Center, Eastern Cooperative Oncology Group, Northwestern University, University of Pennsylvania, Summa Akron City Hospital, Fox Chase Cancer Center, Trinity Health Ann Arbor Hospital, Flatiron Health (United States), Case Comprehensive Cancer Center, Case Western Reserve University
Language: English
Subfield: Epidemiology
Field: Medicine
Domain: Health Sciences
Open Access status: green
Funder: National Cancer Institute
Awards: ECOG Statistical Office Data Management Grant, ECOG-ACRIN Network Group Operations Center, MICHIGAN CANCER RESEARCH CONSORTIUM CCOP, ECOG Clinical Trials, Eastern Cooperative Oncology Group Studies, Eastern Cooperative Oncology Group, ECOG-ACRIN Network Group Statistics and Data Management Center, EASTERN COOPERATIVE ONCOLOGY GROUP - WISCONSIN STUDIES, ECOG Statistical Office, Eastern Cooperative Oncology Group Operations Office, CWRU Case Comprehensive Cancer Center NCTN Lead Academic Participating Site, National Clinical Trials Network Research at the University of Wisconsin, EASTERN COOPERATIVE ONCOLOGY GROUP, ECOG-ACRIN Biospecimen Bank to Support NCTN
OpenAlex ID: W2805803317