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.

Keywords: carcinoid; neuroendocrine tumors.

Conflict of interest statement

Declaration of interest

The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported.

Figures

Figure 1

Waterfall plot illustrating best radiographic response (percent change) in each patient stratified by tumor cohort. (A) Maximum percentage of reduction in sum of tumor diameters from baseline (carcinoid tumor cohort). (B) Maximum percentage of reduction in sum of tumor diameters from baseline (pancreatic NET cohort).

Figure 2

Kaplan–Meier estimate of progression-free survival stratified by tumor cohort.

Figure 3

Kaplan–Meier estimate of overall survival, stratified by tumor cohort.