Anti-VEGF RTKIs Generate Anti-Tumor Effects and Safety in pNETs and epNETs

Treatment with an anti-VEGF tyrosine kinase inhibitor appears safe for patients with pancreatic neuroendocrine tumors and extra-pancreatic neuroendocrine tumors.

Anti-vascular endothelial growth factor (VEGF) receptor tyrosine kinase inhibitor (TKIs) treatment can generate antitumor effects in patients with pancreatic neuroendocrine tumors (pNETs) and extra-pancreatic NETs (epNETs).1

The potential benefit of RTKIs in patients with pNETs and epNETs are based on an evaluation of all phase 2 and phase 3 studies of anti-VEGF TKIs. The results were published in the European Journal of Cancer and support the development of anti-VEGF TKIs in both patient populations. Additionally, these agents appear safe for patients with NETs.

While anti-VEGF TKIs have been studied for their use in patients with neuroendocrine tumors (NETs) over the past few decades, there have not been any trials that have shown their efficacy and toxicity in patients with pNETs and epNETs.

For the analysis, investigators reviewed database information from patients treated between January 1, 2000, and January 31, 2021. The primary objectives that were assessed included comparing objective response rate (ORR) and progression-free survival (PFS) between patients with pNETs and epNETs. Another end point of the analysis is to assess the incidence rate ratio (IRR) of adverse events (AEs) between patients treated with anti-VEGF RTKIs and a control.

There were 92 potentially relevant studies evaluated with 17 included in the meta-analysis with 8 distinct anti-VEGF TKIs. A total of 1611 patients were included, including 1194 patients who were given anti-VEGF TKIs. Among patients with pNETs, the ORR was 18% (95% CI, 13%-25%), compared with an ORR of 8% for patients with epNETs (95% CI, 5%-12%). The test for differences between pNETs and epNETs came out to a P value of < .01).

The median PFS among patients with pNETs was 13.9 months (95% CI, 11.43-16.38 months), vs a median PFS of 12.71 months for patients with epNETs (95% CI, 9.37-16.05 months), for a P value of .55). These data emphasize that there is no difference in PFS between patients with pNETS and epNETS when with an anti-VEGF RTKI.

Looking at safety, one of the most common grade 3 or 4 AEs was hypertension which was observed more in patients who were treated with anti-VEGF TKIs with an IRR of 3.04 (95% CI, 1.63-5.65) compared with patients who received control. Additionally, grade 3 or 4 proteinuria was also observed more in patients treated with an anti-VEGF TKI compared with those given control (IRR 5.79; 95% CI, 1.09-30.74).

Additionally, findings showed that there was no difference in rare serious AEs, including cardiac dysfunction, cerebrovascular accident, myocardial infarction, non-central nervous system bleeding, non-central nervous system emboli, and gastrointestinal tract perforation, between patients given the anti-VEGF TKI and those given the control.

Das S, Phillips S, Lee CL, et al. Efficacy and toxicity of anti-vascular endothelial growth receptor tyrosine kinase inhibitors in patients with neuroendocrine tumours - A systematic review and meta-analysis [published online Jan 11, 2023]. Eur J Cancer. 2023;182:43-52. doi:10.1016/j.ejca.2022.12.031

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