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Everolimus in advanced pancreatic neuroendocrine tumors: the clinical experience

James C Yao1, Alexandria T Phan, Valentine Jehl

  • 1Departments of Gastrointestinal Medical Oncology and Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. jyao@mdanderson.org

Cancer Research
|February 26, 2013
PubMed

Insights

Everolimus, an mTOR inhibitor, delays disease progression in pancreatic neuroendocrine tumors (pNET). Patients progressing on everolimus do not show a more aggressive metastatic phenotype compared to placebo.

Area of Science:

  • Oncology
  • Translational Research
  • Molecular Biology

Background:

  • Neuroendocrine tumor (NET) incidence has risen significantly.
  • New therapies, including everolimus for pancreatic NET (pNET), have emerged.
  • Everolimus demonstrated improved progression-free survival in the RADIANT-3 trial.

Purpose of the Study:

  • Review clinical efficacy of everolimus in pNET.
  • Summarize translational science from clinical studies.
  • Investigate mechanisms of resistance and treatment failure.

Main Methods:

  • Analysis of progression events in the RADIANT-3 study.
  • Comparison of everolimus and placebo arms.
  • Evaluation of metastatic phenotype in patients with disease progression.

Main Results:

  • Fractions of progression events were similar between everolimus and placebo arms.
  • New metastasis only: 21% vs. 22%.
  • Growth of preexisting lesions only: 54% vs. 49%.
  • New metastasis with growth of preexisting lesions: 24% vs. 27%.

Conclusions:

  • Everolimus delays disease progression in pNET.
  • Disease progression on everolimus does not indicate a more aggressive metastatic phenotype.
  • Further research into resistance mechanisms is warranted.

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