Objectives: Well-differentiated neuroendocrine tumors (NET) are highly vascular tumors characterized by their expression of vascular endothelial growth factor (VEGF). This trial investigated the activity of ramucirumab, a monoclonal antibody that targets VEGF receptor-2 (VEGFR-2) and inhibits activity of VEGF, in combination with somatostatin analog therapy in patients (pts) with advanced extra-pancreatic NET.
Methods: We conducted a single-arm phase II trial enrolling pts with advanced, progressive extra-pancreatic NET. Patients were treated with ramucirumab 8 mg/kg intravenously on days 1 and 15 of each 28-day cycle. The primary endpoint was progression-free survival (PFS). Secondary endpoints toxicity, radiographic and biochemical tumor response rate, and overall survival (OS).
Results: The trial enrolled 43 patients. Primary tumor sites included small intestine 20 (46%), lung 10 (23%), thymus 3 (7%), rectum 1(2%), kidney 1(2%), and unknown primary 8(18%). Median PFS was 14.2 months (95% CI, 9.0-25.6 months), and median OS was 24.9 months (95% CI, 20.7-43.1 months). Best response by RECIST 1.1: partial response 5% (95% CI, 0.6%-15.8%). Chromogranin A levels dropped by at least 50% in 10% of the 37 patients who had elevated levels at baseline. Most common all-grade adverse events included fatigue (84%) and hypertension (84%).
Conclusion: Ramucirumab demonstrated efficacy and safety in this single-arm phase II trial. These findings support the continued evaluation of angiogenesis inhibitors in the treatment of NET.
Clinical trial registration: NCT02795858.
Keywords: carcinoid tumors; extrapancreatic neuroendocrine tumors; ramucirumab.
© The Author(s) 2025. Published by Oxford University Press.