1199P MAVERIC: Phase II randomized study of everolimus as maintenance therapy for metastatic neuroendocrine neoplasms (mNEN) with pulmonary or gastroenteropancreatic (GEP) origin. Results on behalf of the GOIRC

NEN are a group of heterogeneous malignancies that most commonly arise in the GEP tract. Usually > 20% Ki-67 NEN, including both well and poorly differentiated, are treated with chemotherapy (CT) but the schedule and duration is debated and no evidence about a maintenance therapy exists. MAVERIC is a randomized, multicentric, phase II trial. Patients (pts) with well/moderately or poorly differentiated mNEN from GEP or lung primary sites with Ki-67 between 20% and 55% in response after a first -line (1L) CT were randomized with a 2:1 ratio to maintenance therapy with everolimus 10 mg day or to observation until progression or treatment intolerance. Randomization was done using a centralized web-based system. The primary endpoint was progression free survival (PFS) and the secondary endpoints were overall survival (OS) and safety. The study design was formally non-comparative. Of 30 patients enrolled between 2015 and 2022 in 5 centers, 20 were randomized to everolimus and 10 to observation; 29 resulted eligible for the analysis. 52% had a GEP and 48% a pulmonary primary site. The median follow-up was 30.3 mo. Median PFS was longer for the experimental arm (1.8 mo vs. 11.4 mo; p=0.022). Median OS was 38.3 and 38.2 mo for the experimental and control arms, respectively (p=0.43). In the experimental arm, G3 adverse events (AEs) occurred in 55% of pts (most commonly mucositis/stomatitis (27.7%) and neutropenia (27.7%)). No G4 AEs occurred. 65% of pts required a dose reduction and 2 pts discontinued treatment due to AEs. This study may suggest a role for everolimus as a maintenance therapy following 1L CT in selected pts with high-grade GEP or lung NEN with Ki67 between 20% and 55%. Homogeneous prospective studies are warranted to validate this hypothesis.