Efficacy of everolimus plus octreotide LAR in patients with advanced neuroendocrine tumor and carcinoid syndrome: final overall survival from the randomized, placebo-controlled phase 3 RADIANT-2 study

Ann Oncol. 2017 Jul 1;28(7):1569-1575. doi: 10.1093/annonc/mdx193.


Background: In the phase 3 RADIANT-2 study, everolimus plus octreotide long-acting repeatable (LAR) showed improvement of 5.1 months in median progression-free survival versus placebo plus octreotide LAR among patients with advanced neuroendocrine tumors associated with carcinoid syndrome. The progression-free survival P-value was marginally above the prespecified threshold for statistical significance. Here, we report final overall survival (OS) and key safety update from RADIANT-2.

Patients and methods: The RADIANT-2 trial compared everolimus (10 mg/day, orally; n = 216) versus placebo (n = 213), both in conjunction with octreotide LAR (30 mg, intramuscularly, every 28 days). Patients, unblinded at the time of progression or after end of double-blind core phase following primary analysis, were offered open-label everolimus with octreotide LAR (open-label phase). In the open-label phase, patients had similar safety and efficacy assessments as those in the core phase. For OS, hazard ratios (HRs) with 95% CIs using unadjusted Cox model and a Cox model adjusted for prespecified baseline covariates were calculated.

Results: A total of 170 patients received open-label everolimus (143 crossed over from the placebo arm; 27 in the everolimus arm continued to receive the same treatment after unblinding). The median OS (95% CI) after 271 events was 29.2 months (23.8-35.9) for the everolimus arm and 35.2 months (30.0-44.7) for the placebo arm (HR, 1.17; 95% CI, 0.92-1.49). HR adjusted for baseline covariates was 1.08 (95% CI, 0.84-1.38). The most frequent drug-related grade 3 or 4 AEs reported during the open-label phase were diarrhea (5.3%), fatigue (4.7%), and stomatitis (4.1%). Deaths related to pulmonary or cardiac failure were observed more frequently in the everolimus arm.

Conclusion: No significant difference in OS was observed for the everolimus plus octreotide LAR and placebo plus octreotide LAR arms of the RADIANT-2 study, even after adjusting for imbalances in the baseline covariates.

Clinical trial number: NCT00412061, www.clinicaltrials.gov.

Keywords: carcinoid syndrome; everolimus; neuroendocrine tumors; overall survival.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Administration, Oral
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Carcinoma, Neuroendocrine / drug therapy*
  • Carcinoma, Neuroendocrine / mortality
  • Carcinoma, Neuroendocrine / pathology
  • Disease Progression
  • Disease-Free Survival
  • Double-Blind Method
  • Drug Administration Schedule
  • Everolimus / administration & dosage*
  • Everolimus / adverse effects
  • Humans
  • Injections, Intramuscular
  • Kaplan-Meier Estimate
  • Malignant Carcinoid Syndrome / drug therapy*
  • Malignant Carcinoid Syndrome / mortality
  • Malignant Carcinoid Syndrome / pathology
  • Octreotide / administration & dosage*
  • Octreotide / adverse effects
  • Proportional Hazards Models
  • Risk Factors
  • Time Factors
  • Treatment Outcome


  • Everolimus
  • Octreotide

Associated data

  • ClinicalTrials.gov/NCT00412061