Adverse Events and Efficacy of Cixutumumab in Phase II Clinical Trials: A systematic Review and Meta-Analysis

Clin Drug Investig. 2017 Feb;37(2):135-153. doi: 10.1007/s40261-016-0475-y.

Abstract

Background and objectives: Cixutumumab is a monoclonal antibody targeting insulin-like growth factor 1 receptor (IGF1R). We sought to evaluate the efficacy of cixutumumab in the treatment of cancer, and to comprehensively assess the associated adverse events in phase II clinical trials.

Methods: Data were collected from PubMed, Embase, and Clinicaltrials.gov. The improvement on progression-free survival (PFS) was evaluated by hazard ratio (HR) and 95% confidence intervals (95% CIs). We also carried a meta-analysis to comprehensively evaluate the incidence of adverse events.

Results: The adverse events that were mentioned most frequently were hyperglycemia, anemia, nausea, fatigue, and thrombocytopenia. The most frequent adverse events were hyponatremia (40.28%), fatigue (35.18%), and skin rash (35.11%). Results showed that cixutumumab treatments did not benefit PFS (HR 1.03, 95% CI 0.83-1.26, p = 0.979). The complete response (CR) was rarely seen in phase II trials.

Conclusions: Cixutumumab was well tolerated when used alone and in combination therapies, but its antitumor activity was low in the existing phase II clinical trials. An acceptable incidence of adverse effects supports further investigation of this drug, provided that it shows antitumor activity in combination with other drugs.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Antibodies, Monoclonal / adverse effects*
  • Antibodies, Monoclonal / therapeutic use*
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents / adverse effects*
  • Antineoplastic Agents / therapeutic use*
  • Clinical Trials, Phase II as Topic*
  • Disease-Free Survival
  • Humans
  • Receptor, IGF Type 1
  • Receptors, Somatomedin / drug effects

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents
  • IGF1R protein, human
  • Receptors, Somatomedin
  • cixutumumab
  • Receptor, IGF Type 1