Pazopanib in pretreated advanced neuroendocrine tumors: a phase II, open-label trial of the Spanish Task Force Group for Neuroendocrine Tumors (GETNE)

Ann Oncol. 2015 Sep;26(9):1987-1993. doi: 10.1093/annonc/mdv252. Epub 2015 Jun 10.

Abstract

Background: The management of advanced neuroendocrine tumors (NETs) has recently changed. We assessed the activity of pazopanib after failure of other systemic treatments in advanced NETs.

Methods: This was a multicenter, open-label, phase II study evaluating pazopanib as a single agent in advanced NETs (PAZONET study). The clinical benefit rate (CBR) at 6 months was the primary end point. Translational correlation of radiological response and progression-free survival (PFS) with circulating and tissue biomarkers was also evaluated.

Results: A total of 44 patients were enrolled. Twenty-five patients (59.5%) were progression-free at 6 months (4 partial responses, 21 stable diseases) with a median PFS of 9.5 months [95% confidence interval (CI) 4.8-14.1]. The CBR varied according to prior therapy received, with 73%, 60% and 25% in patients treated with prior multitarget inhibitors, prior mTOR inhibitors and both agents, respectively. A nonsignificant increase in PFS was observed in patients presenting lower baseline circulating tumor cell (CTC) counts (9.1 versus 5.8 months; P = 0.22) and in those with decreased levels of soluble-vascular endothelial growth factor receptor-2 (sVEGFR-2) (12.6 versus 9.1 months; P = 0.067). A trend toward reduced survival was documented in patients with VEGFR3 rs307821 and rs307826 missense polymorphisms [hazard ratio (HR): 12.3; 95% CI 1.09-139.2; P = 0.042 and HR: 6.9; 95% CI 0.96-49.9; P = 0.055, respectively].

Conclusions: Pazopanib showed clinical activity in patients with advanced NETs regardless of previous treatments. Additionally, CTCs, soluble-s VEFGR-2 and VEGFR3 gene polymorphisms constitute potential biomarkers for selecting patients for pazopanib (NCT01280201).

Clinical trial number: NCT01280201.

Keywords: angiogenic markers; bronchial carcinoids; gastroenteropancreatic tumors; pazopanib; polymorphisms; thymic tumors.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Angiogenesis Inhibitors / adverse effects
  • Angiogenesis Inhibitors / therapeutic use*
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use
  • Biomarkers, Tumor / genetics*
  • Disease-Free Survival
  • Female
  • Humans
  • Indazoles
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Neoplastic Cells, Circulating
  • Neuroendocrine Tumors / drug therapy*
  • Neuroendocrine Tumors / mortality
  • Pancreatic Neoplasms / drug therapy*
  • Pancreatic Neoplasms / mortality
  • Polymorphism, Single Nucleotide / genetics
  • Proportional Hazards Models
  • Pyrimidines / adverse effects
  • Pyrimidines / therapeutic use*
  • Sulfonamides / adverse effects
  • Sulfonamides / therapeutic use*
  • Treatment Outcome
  • Vascular Endothelial Growth Factor Receptor-2 / genetics
  • Vascular Endothelial Growth Factor Receptor-3 / genetics

Substances

  • Angiogenesis Inhibitors
  • Antineoplastic Agents
  • Biomarkers, Tumor
  • Indazoles
  • Pyrimidines
  • Sulfonamides
  • pazopanib
  • KDR protein, human
  • Vascular Endothelial Growth Factor Receptor-2
  • Vascular Endothelial Growth Factor Receptor-3

Associated data

  • ClinicalTrials.gov/NCT01280201