title: A multi-institutional, phase II open-label study of ganitumab (AMG 479) in advanced carcinoid and pancreatic neuroendocrine tumors.
abstract: The IGF pathway has been implicated in the regulation of neuroendocrine tumor (NET) growth, and preliminary studies suggested that ganitumab (AMG 479), a human MAB against IGF1R, may have antitumor activity in this setting. We performed a two-cohort phase II study of ganitumab in patients with metastatic progressive carcinoid or pancreatic NETs (pNETs). This open-label study enrolled patients (≥18 years) with metastatic low- and intermediate-grade carcinoid or pNETs. Inclusion criteria included evidence of progressive disease (by Response Evaluation Criteria in Solid Tumors (RECIST)) within 12 months of enrollment, ECOG PS 0-2, and fasting blood sugar <160  mg/dl. Prior treatments were allowed and concurrent somatostatin analog therapy was permitted. The primary endpoint was objective response. Secondary endpoints included overall survival (OS), progression-free survival (PFS), and safety. Sixty patients (30 carcinoid and 30 pNETs) were treated with ganitumab 18  mg/kg every 3 weeks, among whom 54 patients were evaluable for survival and 53 patients for response. There were no objective responders by RECIST. The median PFS duration was 6.3 months (95% CI, 4.2-12.6) for the entire cohort; 10.5 months for carcinoid patients, and 4.2 months for pNET patients. The OS rate at 12 months was 66% (95% CI, 52-77%) for the entire cohort. The median OS has not been reached. Grade 3/4 AEs were rare and consisted of hyperglycemia (4%), neutropenia (4%), thrombocytopenia (4%), and infusion reaction (1%). Although well tolerated, treatment with single-agent ganitumab failed to result in significant tumor responses among patients with metastatic well-differentiated carcinoid or pNET.
authors.affiliation: Department of GI Oncology, Moffitt Cancer Center, 12902 Magnolia Drive, Tampa, Florida 33612, USA. jonathan.strosberg@moffitt.org
authors.forename: J R
authors.initials: JR
authors.lastname: Strosberg
authors.forename: J A
authors.initials: JA
authors.lastname: Chan
authors.forename: D P
authors.initials: DP
authors.lastname: Ryan
authors.forename: J A
authors.initials: JA
authors.lastname: Meyerhardt
authors.forename: C S
authors.initials: CS
authors.lastname: Fuchs
authors.forename: T
authors.initials: T
authors.lastname: Abrams
authors.forename: E
authors.initials: E
authors.lastname: Regan
authors.forename: R
authors.initials: R
authors.lastname: Brady
authors.forename: J
authors.initials: J
authors.lastname: Weber
authors.forename: T
authors.initials: T
authors.lastname: Campos
authors.forename: L K
authors.initials: LK
authors.lastname: Kvols
authors.forename: M H
authors.initials: MH
authors.lastname: Kulke
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002276:Carcinoid Tumor / Q000188:drug therapy*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D018358:Neuroendocrine Tumors / Q000188:drug therapy*; D010190:Pancreatic Neoplasms / Q000188:drug therapy*; D017526:Receptor, IGF Type 1 / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; C545764:ganitumab; D017526:Receptor, IGF Type 1
keywords: carcinoid; neuroendocrine tumors