Everolimus as maintenance therapy in advanced neuroendocrine neoplasms: Results from the MAVERIC Phase II Trial (1499 WORDS MAIN TEXT)

Background: Neuroendocrine neoplasms (NEN) are a heterogeneous disease and chemotherapy (CT) represents the standard first-line treatment for those with a Ki-67 index >20%. Methods: MAVERIC is a randomized, multicenter, non-comparative phase II study including patients with metastatic gastroenteropancreatic (GEP-NEN) or large-cell neuroendocrine carcinoma (LCNEC) (Ki-67 20%-55%) according to the 2010 WHO grading system and at least stable disease after first-line CT. Patients were randomized (2:1) to everolimus 10 mg/day or observation until progression or treatment intolerance. The primary endpoint was progression-free survival (PFS); secondary endpoints included overall survival (OS) and safety. Results: Between November 2015 and June 2022, 30 patients were enrolled across five Italian centers, with 20 assigned to everolimus and 10 to observation. The analysis included 29 patients (52% GEP-NEN, 48% LCNEC). Median (m)PFS was 11.8 months in the everolimus arm and 1.8 months in the control arm. MOS was similar between arms (38.3 and 38.2 months). The subgroup of 11 patients with GEP-neuroendocrine tumour (NET) grade 3 treated with everolimus showed a mPFS of 19.9 months and mOS of 48.1 months. Most common adverse events (AEs) were mucositis (80%), dyslipidemia (55%), fatigue (45%), pneumonitis (40%), and peripheral edema (35%). Grade 3 AEs occurred in 70% of patients; no grade 4 AEs were observed. Conclusions: The MAVERIC trial demonstrated encouraging clinical benefit of everolimus in metastatic GEP-NEN and LCNEC (Ki-67 20%-55%) following first-line CT. Toxicity was consistent with the known safety profile of everolimus. This strategy was particularly effective in GEP-NEN patients and warrants further investigation.