This is an archive of papers published by the staff and faculty of Fox Chase Cancer Center. For questions about content, please contact Talbot Research Library
Last updated on
Lubner S , Feng Y , Mulcahy M , O'Dwyer P , Giang GY , Hinshaw JL , Deming D , Klein L , Teitelbaum U , Payne J , Engstrom P , Stella P , Meropol N , Benson A
E4206: AMG 706 and Octreotide in Patients with Low-Grade Neuroendocrine Tumors
Oncologist. 2018 Sep;23(9) :1006-e104
PMID: 29853660 PMCID: PMC6192662 URL: https://www.ncbi.nlm.nih.gov/pubmed/29853660
AbstractLESSONS 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.
Notes1549-490x Lubner, Sam Feng, Yang Mulcahy, Mary O'Dwyer, Peter Giang, Guang-Yu Hinshaw, J Louis Deming, Dustin Klein, Leonard Teitelbaum, Ursina Payne, Jennifer Engstrom, Paul Stella, Philip Meropol, Neal Benson, Al Journal Article United States Oncologist. 2018 May 31. pii: theoncologist.2018-0294. doi: 10.1634/theoncologist.2018-0294.