Real-world outcomes of lower lenvatinib doses in advanced neuroendocrine tumors: a multinational retrospective study
G R Almeida1, G K Zanetta1, J M O'Connor2
1AC Camargo Cancer Center, São Paulo, Brazil.
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.
Insights
Lower-dose lenvatinib (10-12 mg/day) effectively treated advanced neuroendocrine tumors (NET) with improved safety. This real-world data supports individualized dosing for better tolerability in GEP and thoracic NET patients.
Area of Science:
- Oncology
- Pharmacology
Background:
- Neuroendocrine tumors (NET) present a growing challenge with limited options for advanced disease.
- Lenvatinib, a multi-targeted tyrosine kinase inhibitor (TKI), shows efficacy but significant toxicity at standard doses.
Purpose of the Study:
- To evaluate the real-world effectiveness and safety of reduced-dose lenvatinib in patients with advanced grade 1-3 gastrointestinal, pancreatic, or thoracic NET.
- To assess if lower lenvatinib doses can maintain antitumor activity while improving tolerability.
Main Methods:
- A retrospective multinational cohort study included 22 patients with advanced NET who received lenvatinib at physician-determined starting doses (8-24 mg/day).
- Primary endpoint was progression-free survival (PFS); secondary endpoints included overall survival (OS) and severe adverse events (AEs).
- Exploratory endpoints assessed objective response rate (ORR) and disease control rate (DCR).
Main Results:
- The median daily lenvatinib dose was 11.8 mg, with a median follow-up of 16.8 months.
- Median PFS was 13 months and median OS was 16 months.
- Objective response rate (ORR) was 31.8% and disease control rate (DCR) was 90.9%. Grade ≥3 adverse events occurred in 22% of patients, with fatigue and hypertension being most common at lower grades.
Conclusions:
- Lenvatinib, at an average daily dose of 10-12 mg, demonstrated significant antitumor activity in advanced GEP and thoracic NET.
- This lower-dose regimen appears to improve tolerability compared to standard dosing, suggesting individualized dosing strategies can balance efficacy and safety.
