Everolimus for the treatment of advanced pancreatic neuroendocrine tumors: Overall survival and circulating biomarkers from the randomized, Phase III RADIANT-3 study

James C. Yao, Marianne Pavel, Catherine Lombard-Bohas, Eric Van Cutsem, Maurizio Voi, Ulrike Brandt, Wei He, David Chen, Jaume Capdevila, Elisabeth G.E. De Vries, Paola Tomassetti, Timothy Hobday, Rodney Pommier, Kjell Öberg

Research output: Contribution to journalArticle

88 Scopus citations

Abstract

Purpose Everolimus improved median progression-free survival by 6.4 months in patients with advanced pancreatic neuroendocrine tumors (NET) compared with placebo in the RADIANT-3 study. Here, we present the final overall survival (OS) data and data on the impact of biomarkers on OS from the RADIANT-3 study. Methods Patients with advanced, progressive, low- or intermediate-grade pancreatic NET were randomly assigned to everolimus 10 mg/day (n = 207) or placebo (n = 203). Crossover from placebo to openlabel everolimus was allowed on disease progression. Ongoing patients were unblinded after final progression-free survival analysis and could transition to open-label everolimus at the investigator's discretion (extension phase). OS analysis was performed using a stratified log-rank test in the intentto- treat population. The baseline levels of chromogranin A, neuron-specific enolase, and multiple soluble angiogenic biomarkers were determined and their impact on OS was explored. Results Of 410 patients who were enrolled between July 2007 and March 2014, 225 received open-label everolimus, including 172 patients (85%) randomly assigned initially to the placebo arm. Median OS was 44.0 months (95% CI, 35.6 to 51.8 months) for those randomly assigned to everolimus and 37.7 months (95% CI, 29.1 to 45.8 months) for those randomly assigned to placebo (hazard ratio, 0.94; 95% CI, 0.73 to 1.20; P = .30). Elevated baseline chromogranin A, neuron-specific enolase, placental growth factor, and soluble vascular endothelial growth factor receptor 1 levels were poor prognostic factors for OS. The most common adverse events included stomatitis, rash, and diarrhea. Conclusion Everolimus was associated with a median OS of 44 months in patients with advanced, progressive pancreatic NET, the longest OS reported in a phase III study for this population. Everolimus was associated with a survival benefit of 6.3 months, although this finding was not statistically significant. Crossover of patients likely confounded the OS results.

Original languageEnglish (US)
Pages (from-to)3906-3913
Number of pages8
JournalJournal of Clinical Oncology
Volume34
Issue number32
DOIs
StatePublished - Nov 10 2016

    Fingerprint

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Yao, J. C., Pavel, M., Lombard-Bohas, C., Van Cutsem, E., Voi, M., Brandt, U., He, W., Chen, D., Capdevila, J., De Vries, E. G. E., Tomassetti, P., Hobday, T., Pommier, R., & Öberg, K. (2016). Everolimus for the treatment of advanced pancreatic neuroendocrine tumors: Overall survival and circulating biomarkers from the randomized, Phase III RADIANT-3 study. Journal of Clinical Oncology, 34(32), 3906-3913. https://doi.org/10.1200/JCO.2016.68.0702