A Phase II Study of Ziv-Aflibercept in Patients With Advanced Extrapancreatic Neuroendocrine Tumors

Pancreas. 2022 Aug 1;51(7):763-768. doi: 10.1097/MPA.0000000000002099.

Abstract

Objectives: Neuroendocrine tumors (NETs) are characterized by their expression of vascular endothelial growth factor (VEGF). This trial investigated the activity of Ziv-aflibercept, a recombinant protein that binds to and inhibits the activity of VEGF, in patients with advanced NETs (NCT01782443).

Methods: A single-arm, phase II trial enrolling patients with advanced, progressive extrapancreatic NET. Patients were treated with Ziv-aflibercept 4 mg/kg intravenously on day 1 and 15 of a 28-day cycle; the starting dose was reduced to 2 mg/kg on days 1 and 15 of a 28-day cycle because of hypertension-related events. The primary end point was progression-free survival.

Results: The trial enrolled 19 patients (13 male:6 female). Patients received a median of 7 cycles (range, 1-18 cycles). The median progression free survival was 11.8 months (95% confidence interval, 3.2-16.1 months), and the median overall survival was 36.4 months (95% confidence interval, 16.1-not reached). Best responses by Response Evaluation Criteria in Solid Tumors 1.1 are as follows: 1 (5%) partial response, 13 (68%) stable disease, 2 (10%) with progressive disease, and 3 (15%) unevaluable. Hypertension occurred in 18 patients (95%), including grade 3-4 hypertension in 12 patients (63%).

Conclusions: Although the progression free survival is similar to other VEGF inhibitors in NET, toxicity may preclude further investigation.

Publication types

  • Clinical Trial, Phase II

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Female
  • Humans
  • Hypertension* / chemically induced
  • Male
  • Neuroendocrine Tumors* / drug therapy
  • Neuroendocrine Tumors* / pathology
  • Vascular Endothelial Growth Factor A

Substances

  • aflibercept
  • Vascular Endothelial Growth Factor A

Associated data

  • ClinicalTrials.gov/NCT01782443