An Italian multicenter phase II trial of metronomic temozolomide in unfit patients with advanced neuroendocrine neoplasms: Interim analysis of the MeTe study

BackgroundTreatment of unfit patients (pts) with neuroendocrine tumors (NETs) represents a major clinical challenge with limited evidence. Therefore, we aimed to investigate the activity and safety of metronomic temozolomide (mTEM) in unfit pts with advanced gastroenteropancreatic (GEP) and lung NET in order to spare toxicities and benefit of its antiangiogenic effect.MethodsThis is a non-planned first interim analysis of an Italian, multicenter, open-label, non-randomized, phase II trial. Unfit patients, defined according to ECOG performance status (PS) and/or comorbidity and/or organ function and/or number of previous treatments received mTEM 60 mg daily continuously. The primary endpoint was the progression free survival (PFS) calculated by the Kaplan-Meier product-limit method. The secondary endpoints included: objective response rate (ORR), disease control rate (DCR), overall survival (OS), safety, clinical response, and quality of life (QoL) based on QLQ-C30, QLQ-GINET21, and G8 score analyses. The immunohistochemical determination of the O6-methylguanine-DNA methyltransferase (MGMT) represents an exploratory endpoint.ResultsAt December 2023, 20/46 pts were included and 18 were evaluable. The majority had an advanced GEP NET, mostly G2 (39%). The most represented primary sites were pancreas (33%), lung (28%), ileum (22%), rectum (6%), unknown (6%), and duodenum (5%). There were 7/18 (40%) pts with PS 2 ECOG, 14/18 (78%) with at least one severe comorbidity, and 9/18 (50%) with moderate renal function. More than half population received mTEM as second or third line of therapy. Median number of mTEM cycles was 8. After a median 9-month follow-up, mPFS and mOS were not reached. The 5-month PFS and OS rate were 71% and 83%, respectively. In our cohort, ORR was 6% and DCR 88%. Clinical stability and ECOG PS recovery were the main clinical responses. The treatment was well tolerated without a 3-month QoL impairment.ConclusionsThis non-planned interim analysis of the MeTe study shows signs of activity and safety in unfit pts with advanced NET. Moreover, the preserved QoL, represent a relevant key advantage of this strategy. Based on these promising data, the study is currently ongoing.Clinical trial identificationNCT05554003.Legal entity responsible for the studyThe authors.FundingIstituto Europeo di Oncologia (IEO), IRCCS, Milan.DisclosureF. 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, Other, Steering committee: Novartis; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Advisory Board: Merck, MSD, Novartis, Ipsen; Financial Interests, Institutional, Local PI: Astellas, MSD, Beigene, Nucana, Ipsen, Fibrogen, ITM, Boehringer; Financial Interests, Institutional, Research Grant: Ipsen, Novartis, 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 NET Faculty: ESMO; Non-Financial Interests, Other, Internal reviewer of NET guidelines: AIOM. All other authors have declared no conflicts of interest.