Cancer Res Treat.  2017 Oct;49(4):851-868. 10.4143/crt.2016.176.

Anti-angiogenic Therapy in Patients with Advanced Gastric and Gastroesophageal Junction Cancer: A Systematic Review

Affiliations
  • 1National Institute of Cancer Research, National Health Research Institutes and National Cheng Kung University Hospital, National Cheng Kung University, Tainan, Taiwan.
  • 2Division of Medical Oncology, Department of Internal Medicine, Seoul National University Hospital, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.
  • 3Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea. ykkang@amc.seoul.kr
  • 4Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan.
  • 5Department of Clinical Oncology, The Chinese University of Hong Kong, Hong Kong, China.
  • 6Eli Lilly and Company, Sesto Fiorentino, Florence, Italy.
  • 7Eli Lilly and Company, Taipei, Taiwan.
  • 8Eli Lilly and Company, Indianapolis, IN, USA.
  • 9Eli Lilly and Company, Buenos Aires, Argentina.

Abstract

Despite advancements in therapy for advanced gastric and gastroesophageal junction cancers, their prognosis remains dismal. Tumor angiogenesis plays a key role in cancer growth and metastasis, and recent studies indicate that pharmacologic blockade of angiogenesis is a promising approach to therapy. In this systematic review, we summarize current literature on the clinical benefit of anti-angiogenic agents in advanced gastric cancer. We conducted a systematic search of PubMed and conference proceedings including the American Society of Clinical Oncology, the European Society for Medical Oncology, and the European Cancer Congress. Included studies aimed to prospectively evaluate the efficacy and safety of anti-angiogenic agents in advanced gastric or gastroesophageal junction cancer. Each trial investigated at least one of the following endpoints: overall survival, progression-free survival/time to progression, and/or objective response rate. Our search yielded 139 publications. Forty-two met the predefined inclusion criteria. Included studies reported outcomes with apatinib, axitinib, bevacizumab, orantinib, pazopanib, ramucirumab, regorafenib, sorafenib, sunitinib, telatinib, and vandetanib. Second-line therapy with ramucirumab and third-line therapy with apatinib are the only anti-angiogenic agents so far shown to significantly improve survival of patients with advanced gastric cancer. Overall, agents that specifically target the vascular endothelial growth factor ligand or receptor have better safety profile compared to multi-target tyrosine kinase inhibitors.

Keyword

Angiogenesis inhibitors; Esophagogastric junction; Stomach neoplasms; Vascular endothelial growth factors

MeSH Terms

Angiogenesis Inhibitors
Bevacizumab
Disease-Free Survival
Esophagogastric Junction*
Humans
Medical Oncology
Neoplasm Metastasis
Prognosis
Prospective Studies
Protein-Tyrosine Kinases
Stomach Neoplasms
Vascular Endothelial Growth Factor A
Vascular Endothelial Growth Factors
Angiogenesis Inhibitors
Bevacizumab
Protein-Tyrosine Kinases
Vascular Endothelial Growth Factor A
Vascular Endothelial Growth Factors

Figure

  • Fig. 1. PRISMA flow diagram. OS, overall survival; PFS, progression-free survival; TTP, time to progression; ORR, objective response rate.


Reference

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