Real-world outcomes of lower lenvatinib doses in advanced neuroendocrine tumors: a multinational retrospective study.

Objective: Neuroendocrine tumors (NET) are heterogeneous neoplasms with increasing incidence and limited treatment options for advanced, progressive disease. Lenvatinib, a multitargeted TKI, demonstrated high efficacy but substantial toxicity at the standard 24 mg/day in the phase II TALENT trial. This study evaluates real-world efficacy and safety of lower-dose lenvatinib in patients with grade 1-3 GEP or thoracic NET. Design: Retrospective multinational cohort study. Methods: Twenty-two patients from Brazil, Argentina, and Israel with grade 1-3 NET and radiologic progression received lenvatinib (starting doses per physician discretion) between March 2021 and September 2024. The primary endpoint was progression-free survival (PFS); secondary endpoints were overall survival (OS) and grade ≥3 adverse events (AEs). Exploratory endpoints included objective response rate (ORR) and disease control rate (DCR). Kaplan-Meier methods estimated time-to-event outcomes; AEs were graded per CTCAE v5.0. Results: Median age was 60 years (range: 36-81); primary sites were pancreatic (27%), gastrointestinal (54.5%), and thoracic (18.2%). Grades: G1 (23%), G2 (45%), G3 (31.8%). Starting doses ranged 8-24 mg/day, most often 10 mg (32%) or 8 mg (27%); 45% required reductions. Mean daily dose was 11.8 mg (±4.7). After 16.8 months median follow-up, mPFS was 13 months (IQR: 8.8-17.9) and mOS 16 months (IQR: 12.6-18.5). Among 22 evaluable patients, ORR was 31.8% and DCR 90.9%. Grade 3-4 AEs occurred in 22%; most were grade 1-2 (fatigue 31.8%, hypertension 22.7%). Conclusions: Lenvatinib (average of 10-12 mg/day) showed meaningful antitumor activity and improved tolerability in advanced GEP and thoracic NET, supporting individualized dosing to enhance safety without compromising efficacy.