The Efficacy of a Lower Dose of Everolimus in Patients with Advanced Neuroendocrine Tumors.

Background: Everolimus at 10 mg daily is approved to treat patients with advanced grade 1/2 neuroendocrine tumors (NETs), although it may lead to significant toxicity. Grade 3 or higher drug-related adverse events and drug discontinuation occur in approximately one-fourth of cases. However, phase I trials have demonstrated that doses from 5 mg daily efficiently inhibit NET cell signaling.

Objectives And Methods: This multicenter retrospective study compared the time to treatment failure (TTF) in patients with NETs who received a mean daily dose of 7-10 mg (higher dose [HD]) or ≤6 mg (lower dose [LD]) of everolimus.

Results: Ninety-two patients were included: 74 (80%) in the HD group and 18 (20%) in the LD group. At a median follow-up of 4.2 years, the median time to treatment failure (TTF) was 9.2 months for the HD and 7.2 months for the LD groups ( = 0.85). The TTF did not significantly differ between the LD and the HD groups (HR: 1.24; 95% CI: 0.68-2.25; = 0.47), even after adjusting for age at treatment initiation, the NET grade, and the treatment line.

Conclusion: Everolimus doses from 5 to 6 mg/day seem to be equally as effective as higher doses, but lower doses are potentially associated with less toxicity and lower costs. These findings support validation through a randomized clinical trial.