The adverse events profile of anti-IGF-1R monoclonal antibodies in cancer therapy

Br J Clin Pharmacol. 2014 Jun;77(6):917-28. doi: 10.1111/bcp.12228.

Abstract

Aim(s): Insulin-like growth factor-1 receptor (IGF-1R) targeted therapies have become one of the intriguing areas in anticancer drug development during the last decade. As one of these therapies, anti-IGF-1R monoclonal antibodies (mAbs) are also advancing further in development. Our purpose was to conduct a systematic review of the adverse events (AEs) caused by anti-IGF-1R monoclonal antibodies in cancer therapy.

Methods: We searched the term'IGF-1R monoclonal antibody' in the Pubmed database and found 389 related articles. After elaborate selection, 15 clinical studies that satisfied our criteria were then adopted for further analysis. We extracted all the useful information about the AEs of mAbs from the enrolled studies. Every kind of reported AE as well as corresponding incidences were summed up and calculated. We compared AE incidence differences in two age groups, and analyzed toxicities of mAbs used as a single agent or combined with chemotherapies. Finally, the differences of AE profiles between individual mAbs were also valued.

Results: AEs were more severe in the lower age group and 13 of 19 AE incidences in the single-agent group were significantly lower than in the combination group (P < 0.05). R1507 seemed to show a worse AE profile than cixutumumab and figitumumab.

Conclusions: When anti-IGF-1R mAbs are used for cancer therapy, it is essential to choose the proper drug and combined chemotherapies to reduce AE occurrences. Also, administration of these mAbs to younger patients should be more carefully supervised. Furthermore, some more frequently observed AEs for specific mAb should be paid adequate attention.

Keywords: R1507; adverse events; anti-IGF-1R monoclonal antibody; cixutumumab; dalotuzumab; figitumumab.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review
  • Systematic Review

MeSH terms

  • Animals
  • Antibodies, Monoclonal / adverse effects*
  • Antibodies, Monoclonal, Humanized
  • Cardiotoxicity / etiology
  • Humans
  • Hyperglycemia / chemically induced
  • Neoplasms / drug therapy*
  • Neutropenia / chemically induced
  • Receptor, IGF Type 1 / immunology*
  • Thrombocytopenia / chemically induced

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • cixutumumab
  • Receptor, IGF Type 1
  • figitumumab
  • teprotumumab