Impact of multikinase inhibitors in reshaping the treatment of advanced gastroenteropancreatic neuroendocrine tumors

PMCID: PMC12177888

PMID: 40392078

DOI: 10.1530/ERC-25-0052

Journal: Endocrine-related cancer

Publication Date: 2025-6-18

Authors: Siebenhüner AR, Refardt J, Nicolas GP, Kaderli R, Walter MA, et al.

Key Points

• MKIs represent a significant advancement in GEP-NET treatment, offering improved progression-free survival across multiple tumor subtypes
• Median PFS improvements range from 5.5-10.9 months, with some studies showing up to 52% reduction in progression risk
• Careful patient monitoring and toxicity management are crucial, given the 60-98% rate of adverse events observed across clinical trials

Summary

This comprehensive review explores the evolving landscape of multikinase inhibitor (MKI) treatments for advanced gastroenteropancreatic neuroendocrine tumors (GEP-NETs), highlighting the critical need for more effective management strategies. The analysis reveals significant progress in systemic treatments, with MKIs demonstrating improved progression-free survival (PFS) across multiple NET subtypes, particularly in pancreatic NETs. Despite the promising clinical outcomes, the treatment approach remains complex, characterized by substantial inter-patient variability and challenging toxicity profiles.

The review synthesizes evidence from pivotal clinical trials, showcasing the effectiveness of agents like everolimus, sunitinib, surufatinib, and cabozantinib in extending patient progression-free survival. Notably, these MKIs have shown median PFS improvements ranging from 5.5 to 10.9 months compared to placebo, with some studies reporting 52% reduction in progression risk. The research underscores the importance of careful patient selection, proactive adverse event management, and the potential for personalized treatment strategies as the field continues to evolve.