Update of IGF-1 receptor inhibitor (ganitumab, dalotuzumab, cixutumumab, teprotumumab and figitumumab) effects on cancer therapy

Oncotarget. 2017 Apr 25;8(17):29501-29518. doi: 10.18632/oncotarget.15704.

Abstract

Background: Prognostic studies of insulin-like growth factor-1 receptor(IGF-1R) inhibitors in cancer therapy had promising results in infratests, which exhibited that IGF-1R signalling was crucial in cancer cells growth. However, the conclusion of later clinical trials revealed a dim future for IGF-1R inhibitors to treat cancer. We conducted this analysis to figure out how IGF-1R inhibitors acted in clinical cancer therapy.

Material and methods: We searched up-to-date studies about the single agent of IGF-1R inhibitors or combination with other therapies in solid tumor. Five IGF-1R anti-agents were involved. The primary endpoint was progression-free survival (PFS). The secondary endpoint was overall survival (OS).

Result: 17studies were enrolled. The results was not significant in overall survival (I2=37.1%, P=0.080, HR=1.08, 95% CI=0.97-1.21) and in progression-free survival (I2=0.0%, P=0.637, HR=1.05, 95% CI=0.98-1.12). OS for dalotuzumab, breast cancer, colorectal cancer, and PFS for prostate cancer even indicated harmful effects.

Conclusion: So far, anti-IGF-1R mono-antibodies did not make significant differences in solid tumor prognosis. On the contrary, pessimistic effects were shown in the dalotuzumab, breast cancer, colorectal cancer and prostate cancer subgroups. Further studies of IGF-1R anti-agents were needed, but unwarranted in unselected patients by predictive biomarkers.

Keywords: IGF-1R; cancer treatment; combination chemotherapy; curative effects; prognostic clinical trials.

Publication types

  • Review

MeSH terms

  • Aged
  • Humans
  • Middle Aged
  • Neoplasms / drug therapy*
  • Neoplasms / mortality
  • Neoplasms / pathology
  • Prognosis
  • Receptor, IGF Type 1 / antagonists & inhibitors*
  • Survival Analysis

Substances

  • Receptor, IGF Type 1