Efficacy and toxicity of anti-vascular endothelial growth receptor tyrosine kinase inhibitors in patients with neuroendocrine tumours – A systematic review and meta-analysis

• Published in: European journal of cancer (1990) 2023-03, Vol.182, p.43-52
• Main Authors: Das, Satya, Phillips, Sharon, Lee, Cody L., Agarwal, Rajiv, Bergsland, Emily, Strosberg, Jonathan, Chan, Jennifer A., LaFerriere, Heather, Ramirez, Robert A., Berlin, Jordan, Dasari, Arvind
• Format: Article
• Language: English
• Subjects: Anti-vascular endothelial growth factor; Humans; Neuroectodermal Tumors, Primitive; Neuroendocrine Tumors - pathology; Neuroendocrine tumours; Objective response rate; Progression-free survival; Receptor Protein-Tyrosine Kinases; Receptor tyrosine kinase inhibitors; Systematic review & meta-analysis; Toxicity; Tyrosine Kinase Inhibitors
• ISSN: 0959-8049; 1879-0852
• DOI: 10.1016/j.ejca.2022.12.031

Although anti-vascular endothelial growth factor (VEGF) receptor tyrosine kinase inhibitors (RTKIs) have been tested in patients with neuroendocrine tumours (NETs) over the last two decades, no study to date has benchmarked efficacy and toxicity of these drugs in this patient population. All phase II and phase III studies of anti-VEGF RTKIs in patients with NETs, published between January 1, 2000 andJuly 31, 2021, across major trial databases, were searched in August 2021 for relevant studies. The primary objectives of the meta-analysis were to compare objective response rate (ORR) and progression-free survival (PFS) between patients with pancreatic NETs (pNETs) and extra-pancreatic NETs (epNETs), and the incidence rate ratio (IRR) of adverse events between patients receiving anti-VEGF RTKIs and control. 1611 patients were available for the meta-analysis; 1194 received anti-VEGF RTKIs. ORR in pNETs was 18% (95% confidence interval (CI) 13–25%), while ORR in epNETs was 8% (95% CI 5–12%); test for differences between pNETs and epNETs (x12 = 8.38, p