Phase II trial of VEGFR2 inhibitor apatinib for metastatic sarcoma: focus on efficacy and safety

Exp Mol Med. 2019 Feb 28;51(3):1-11. doi: 10.1038/s12276-019-0221-7.

Abstract

Apatinib (YN968D1) is a novel tyrosine kinase inhibitor targeting vascular endothelial growth factor receptor 2 (VEGFR-2). We conducted a single-arm, nonrandomized phase II study (NCT03121846) to assess the efficacy and safety of apatinib in patients with stage IV sarcoma. We recruited 64 patients with stage IV sarcoma who had failed chemotherapy. The primary endpoint was progression-free survival (PFS), and the secondary endpoints were progression-free survival rate (PFR), objective response rate (ORR), and disease control rate (DCR) at week 12. Treatment-related adverse effects (AEs) were evaluated. Fifty-nine patients were assessed for efficacy and 64 patients for AEs. The median PFS was 7.93 months. At 12 weeks, the PFR was 74%, the ORR was 16.95% (10/59), and the DCR was 86.44% (51/59). The final ORR was 15.25% (9/59) and the DCR was 57.63% (34/59). Notably, 22 patients (34.38%) who developed hypertension, hand-foot-skin reaction, or proteinuria had significantly longer OS than those without these AEs (18.20 vs. 10.73 months; P = 0.002). We conclude that apatinib is effective and well tolerated in patients with advanced sarcoma. The development of hypertension, hand-foot-skin reaction, or proteinuria may indicate a favorable prognosis, representing a novel finding in sarcoma patients.

Publication types

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

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use*
  • Child
  • Female
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Metastasis / drug therapy
  • Neoplasm Metastasis / pathology
  • Progression-Free Survival
  • Protein Kinase Inhibitors / adverse effects
  • Protein Kinase Inhibitors / therapeutic use*
  • Pyridines / adverse effects
  • Pyridines / therapeutic use*
  • Sarcoma / drug therapy*
  • Sarcoma / pathology
  • Treatment Outcome
  • Vascular Endothelial Growth Factor Receptor-2 / antagonists & inhibitors*
  • Young Adult

Substances

  • Antineoplastic Agents
  • Protein Kinase Inhibitors
  • Pyridines
  • apatinib
  • KDR protein, human
  • Vascular Endothelial Growth Factor Receptor-2