Everolimus in Neuroendocrine Tumors of the Gastrointestinal Tract and Unknown Primary

Simron Singh, Carlo Carnaghi, Roberto Buzzoni, Rodney F. Pommier, Markus Raderer, Jiri Tomasek, Harald Lahner, Juan W. Valle, Maurizio Voi, Lida Bubuteishvili-pacaud, Jeremie Lincy, Edward Wolin, Natsuko Okita, Steven K. Libutti, Do-youn Oh, Matthew Kulke, Jonathan Strosberg, James C. Yao, Marianne E. Pavel, Nicola Fazio

Research output: Contribution to journalArticlepeer-review

421 Downloads (Pure)


Purpose: The RADIANT-4 randomized phase 3 study demonstrated significant prolongation of median progression-free survival (PFS) with everolimus compared to placebo (11.0 [95% CI 9.2-13.3] vs. 3.9 [95% CI 3.6-7.4] months) in patients with advanced, progressive, nonfunctional gastrointestinal (GI) and lung neuroendocrine tumors (NET). This analysis specifically evaluated NET patients with GI and unknown primary origin.
Methods: Patients in the RADIANT-4 trial were randomized 2:1 to everolimus 10 mg/day or placebo. The effect of everolimus on PFS was evaluated in patients with NET of the GI tract or unknown primary site.
Results: Of the 302 patients enrolled, 175 had GI NET (everolimus, 118; placebo, 57) and 36 had unknown primary (everolimus, 23; placebo, 13). In the GI subset, the median PFS by central review was 13.1 months (95% CI 9.2-17.3) in the everolimus arm versus 5.4 months (95% CI 3.6-9.3) in the placebo arm; the hazard ratio (HR) was 0.56 (95% CI 0.37-0.84). In the unknown primary patients, the median PFS was 13.6 months (95% CI 4.1-not evaluable) for everolimus versus 7.5 months (95% CI 1.9-18.5) for placebo; the HR was 0.60 (95% CI 0.24-1.51). Everolimus efficacy was also demonstrated in both midgut and non-midgut populations; a 40-46% reduction in the risk of progression or death was reported for patients in the combined GI and unknown primary subgroup. Everolimus had a benefit regardless of prior somatostatin analog therapy. Conclusions: Everolimus showed a clinically meaningful PFS benefit in patients with advanced progressive nonfunctional NET of GI and unknown primary, consistent with the overall RADIANT-4 results, providing an effective new standard treatment option in this patient population and filling an unmet treatment need for these patients.
Original languageEnglish
Pages (from-to)211-220
Issue number3
Early online date24 May 2017
Publication statusPublished - 1 Apr 2018

Research Beacons, Institutes and Platforms

  • Manchester Cancer Research Centre


Dive into the research topics of 'Everolimus in Neuroendocrine Tumors of the Gastrointestinal Tract and Unknown Primary'. Together they form a unique fingerprint.

Cite this