Everolimus in advanced, progressive, well-differentiated, non-functional neuroendocrine tumors: RADIANT-4 lung subgroup analysis

Nicola Fazio, Roberto Buzzoni, Gianfranco Delle Fave, Margot E. Tesselaar, Edward Wolin, Eric Van Cutsem, Paola Tomassetti, Jonathan Strosberg, Maurizio Voi, Lida Bubuteishvili-Pacaud, Antonia Ridolfi, Fabian Herbst, Jiri Tomasek, Simron Singh, Marianne Pavel, Matthew H. Kulke, Juan W. Valle, James C. Yao

Research output: Contribution to journalArticlepeer-review

63 Scopus citations


In the phase III RADIANT-4 study, everolimus improved median progression-free survival (PFS) by 7.1 months in patients with advanced, progressive, well-differentiated (grade 1 or grade 2), non-functional lung or gastrointestinal neuroendocrine tumors (NETs) vs placebo (hazard ratio, 0.48; 95% confidence interval [CI], 0.35-0.67; P <.00001). This exploratory analysis reports the outcomes of the subgroup of patients with lung NETs. In RADIANT-4, patients were randomized (2:1) to everolimus 10 mg/d or placebo, both with best supportive care. This is a post hoc analysis of the lung subgroup with PFS, by central radiology review, as the primary endpoint; secondary endpoints included objective response rate and safety measures. Ninety of the 302 patients enrolled in the study had primary lung NET (everolimus, n = 63; placebo, n = 27). Median PFS (95% CI) by central review was 9.2 (6.8-10.9) months in the everolimus arm vs 3.6 (1.9-5.1) months in the placebo arm (hazard ratio, 0.50; 95% CI, 0.28-0.88). More patients who received everolimus (58%) experienced tumor shrinkage compared with placebo (13%). Most frequently reported (≥5% incidence) grade 3-4 drug-related adverse events (everolimus vs. placebo) included stomatitis (11% vs. 0%), hyperglycemia (10% vs. 0%), and any infections (8% vs. 0%). In patients with advanced, progressive, well-differentiated, non-functional lung NET, treatment with everolimus was associated with a median PFS improvement of 5.6 months, with a safety profile similar to that of the overall RADIANT-4 cohort. These results support the use of everolimus in patients with advanced, non-functional lung NET. The trial is registered with ClinicalTrials.gov (no. NCT01524783).

Original languageEnglish (US)
Pages (from-to)174-181
Number of pages8
JournalCancer Science
Issue number1
StatePublished - Jan 2018


  • everolimus
  • lung carcinoid
  • neuroendocrine tumors
  • progression-free survival

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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