EVENET: Randomised phase II trial of everolimus 5mg vs. 10mg daily in patients with neuroendocrine tumours

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Introduction: Everolimus 10mg PO daily is approved for patients (pts) with advanced G1/G2 neuroendocrine tumours (NET) but is associated with significant toxicity, including 20% of serious infections in real-world pts. In phase I trials, 5mg/day was sufficient to inhibit the mTOR pathway. Retrospective data suggest that 5mg/day is similarly effective to 10mg/day but less toxic.

Aim(s): To evaluate whether everolimus 5mg/day is as effective, but safer, as 10mg/day for patients with advanced NET.

Materials and methods: Randomised, open-label, multicentre phase II near-equivalence clinical trial of everolimus 5mg vs. 10mg oral/day continuously in pts. with metastatic and progressive GEP/lung NET. Eligible pts. must have received > 1 line of therapy, have radiological progression < 6 months, measurable G1/G2 NET, good organ function. Concomitant use of somatostatin analogue is allowed for pts. with functioning NET. Exclusion criteria: Aggressive disease requiring cytotoxic therapy or uncontrolled comorbid conditions. The primary endpoint is progression-free survival (PFS) rate at 12 months; secondary endpoints are progression-free survival, time to treatment failure, objective response, and toxicity. Pts. are randomised 1: 1 and stratified by line of everolimus (1st or 2nd vs ≥ 3rd), primary site (pancreas vs. GI/lung), and Ki-67 (< 10% vs. ≥ 10%). The planned sample size is 100, assuming an H0 of 50% PFS rate at 12 months, H1 42% PFS rate at 12 months (based on the inferior value of the 95% Confidence Interval of everolimus arms of RADIANT trials); one-sided alpha error of 5%, beta error of 10% and an attrition rate of 20%. Sponsorship: Everolimus is provided by the local health care system, as a standard medication, Trial number: NCT06472388.

Conference:

Presenting Author:

Authors: Riechelmann R, Campos A, Durant L, Bulzico D,

Keywords: everolimus, neuroendocrine tumour, dose optimisation, toxicity,