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

Background

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.

Methods

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.

Results

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.

Conclusions

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.

Clinical trial identification

EudraCT n. 2014-003951-72.

Editorial acknowledgement

Legal entity responsible for the study

Lorenzo Antonuzzo.

Funding

Has not received any funding.

Disclosure

L. Antonuzzo: Financial Interests, Personal, Advisory Board: AstraZeneca, Pfizer, Roche, Lilly, BMS, MSD, Merck, Amgen. F. Spada: Financial Interests, Personal, Invited Speaker: Advanced Accelerator Applications, SAS SPA; Financial Interests, Personal, Writing Engagement: Ipsen, Merck, Advanced Accelerator Applications; Non-Financial Interests, Project Lead, Coordinator of neuroendocrine neoplasms guidelines: AIOM (Italian Association Of Medical Oncology); Non-Financial Interests, Leadership Role, I am member of Scientific Board and lead of neuroendocrine Neoplasms Guidelines: ITANET (Italian Association Of Medical Oncology). N. Fazio: Financial Interests, Personal, Advisory Board: Novartis, Merck, AAA, Hutchinson MediPharma, MSD; Financial Interests, Personal, Invited Speaker: AAA, Merck; Financial Interests, Institutional, Local PI: Astellas, MSD, BeiGene, Incyte, Nucana, Ipsen, 4SC, Fibrogen; Financial Interests, Institutional, Research Grant: IPSEN, AAA, Merck; Non-Financial Interests, Other, Steering committee: SPARC Europe; Non-Financial Interests, Member of Board of Directors: ENETS; Non-Financial Interests, Other, Member of the GI and NET Faculties: ESMO; Non-Financial Interests, Other, Internal reviewer of NET guidelines: AIOM. All other authors have declared no conflicts of interest.