A Pilot Study of Apatinib as Third-Line Treatment in Patients With Heavily Treated Metastatic Colorectal Cancer

Clin Colorectal Cancer. 2018 Sep;17(3):e443-e449. doi: 10.1016/j.clcc.2018.02.011. Epub 2018 Mar 2.

Abstract

Background: Antiangiogenic therapy has shown improved clinical outcome in metastatic colorectal cancer (mCRC). After the failure of standard treatments, regorafenib and TAS-102 would be recommended for patients with mCRC, however, they have not been approved in China during this study period.

Patients and methods: This pilot study aimed to assess the efficacy and safety of apatinib, a novel oral inhibitor targeting vascular endothelial growth factor receptor 2, as third-line treatment for patients with mCRC refractory to standard therapies. In this retrospective study, all patients received apatinib treatment until progressive disease (PD), death, unacceptable toxicity, and curative surgery. The dose or treatment schedule was modified according to the physician's discretion according to the toxicity profiles.

Results: Between March 2015 and June 2017, 36 patients were enrolled and eligible for evaluation of the safety and efficacy. One patient (2.8%) achieved complete response, 3 (8.3%) achieved partial response, 24 (66.7%) achieved stable disease, and 8 (22.2%) PD. The objective response rate and the disease control rate were 11.1% (4 of 36), and 77.8% (28 of 36), respectively. Moreover, the median overall survival (OS) since the initiation of first-line treatment was 33.2 months. The median progression-free survival (PFS) and median OS from apatinib treatment were 4.8 and 10.1 months, respectively. Intergroup analysis showed that there was no significant difference in median PFS and median OS between patients who were previously treated with and without bevacizumab. The most common Grade 3 to 4 adverse reactions were hand-foot syndrome, hypertension, and proteinuria.

Conclusion: Our results suggested that apatinib was active as a third-line treatment of refractory mCRC with a manageable tolerability profile. In addition, preliminary data suggested that the efficacy of apatinib would not be affected by previous bevacizumab treatment. Further prospective randomized controlled clinical trials are urgently needed.

Keywords: Angiogenesis; Apatinib; Chemotherapy; Metastatic colorectal cancer; Third-line therapy.

MeSH terms

  • Administration, Oral
  • Adult
  • Aged
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use*
  • Bevacizumab / pharmacology
  • Bevacizumab / therapeutic use
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / mortality
  • Colorectal Neoplasms / pathology
  • Drug Resistance, Neoplasm
  • Female
  • Hand-Foot Syndrome / epidemiology
  • Hand-Foot Syndrome / etiology
  • Humans
  • Hypertension / chemically induced
  • Hypertension / epidemiology
  • Male
  • Middle Aged
  • Pilot Projects
  • Progression-Free Survival
  • Protein Kinase Inhibitors / pharmacology
  • Protein Kinase Inhibitors / therapeutic use*
  • Proteinuria / chemically induced
  • Proteinuria / epidemiology
  • Pyridines / pharmacology
  • Pyridines / therapeutic use*
  • Retrospective Studies
  • Treatment Failure
  • Vascular Endothelial Growth Factor Receptor-2 / antagonists & inhibitors

Substances

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