Lenvatinib as salvage therapy in advanced and progressive GI-NET

The efficacy of lenvatinib in treating gastrointestinal neuroendocrine tumors (GI-NETs) has been explored in preclinical studies and early-phase clinical trials, but real-world data remain limited. Data of sixteen patients (median age 65 years; 62.5% female) with advanced and progressive GI-NET who were treated with lenvatinib at the ENETS Center, University Hospital Essen, between July 2019 and February 2024 were analyzed. Patients received all other approved therapies and showed progression within 2 months. Salvage therapy with lenvatinib was initiated after approval from health insurance. Most NETs originated in the small intestine (94%) with a median Ki-67 index of 3.5%. Before lenvatinib, patients received a median of four lines of treatment (range 3-7), including somatostatin analogs (100%), everolimus (100%), chemotherapy (25%) and PRRT (88%). Surgery of the primary and/or metastatic lesions was performed in 81% and ablative therapies in 38%. The median time between NET diagnosis and the initiation of lenvatinib was 100 months. The overall response rate on salvage therapy was 29% and the clinical benefit rate was 100%. The median progression-free survival (PFS) on lenvatinib was 10 months and the median overall survival (OS) after the initiation of lenvatinib reached 113 months. Hypertension was associated with significantly longer PFS (24.5 months, P = 0.007), whereas weight loss correlated with shorter PFS (4 months, P = 0.0032). In this retrospective single-center case analysis, lenvatinib demonstrated promising results in heavily pre-treated and rapidly progressing GI-NET. With an OS of 9.4 years after start of salvage therapy, these results highlight the value of lenvatinib as a therapeutic option for advanced GI-NET patients with otherwise limited treatment alternatives.