A new study published in Acta Clinica Belgica has found that vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKIs) can produce substantial tumor shrinkage in patients with metastatic clear-cell renal cell carcinoma (ccRCC) involving the pancreas.
The findings are particularly notable for patients whose pancreatic or thyroid metastases require effective local control. Researchers from University Hospitals Leuven and collaborating institutions found that treatment regimens containing a VEGFR-TKI produced better tumor responses than immune checkpoint inhibitor therapy alone.
Axitinib appeared to drive tumor response
The researchers first examined five patients with pancreatic metastases who received axitinib plus pembrolizumab as first-line treatment.
In these cases, tumor control repeatedly tracked with the use and dose of axitinib. When axitinib was reduced or temporarily stopped, the metastases generally began to progress. When the drug was restarted or its dose increased, disease control returned. In four of the five patients, progression occurred even though pembrolizumab was still being administered.
The pattern was also illustrated in individual patient cases. For example, in one patient, repeated axitinib interruptions were followed by tumor growth, while restarting the drug resulted in renewed tumor response.
Combination therapy produced the greatest tumor shrinkage
The researchers then evaluated 119 individual pancreatic metastases treated under different therapeutic settings.
The analysis showed that pronounced tumor shrinkage was mainly seen when a VEGFR-TKI was part of treatment.
Among 40 patients with pancreatic and/or thyroid metastases, the response rates were:
83% with an immune checkpoint inhibitor (ICPI) plus VEGFR-TKI
69% with VEGFR-TKI monotherapy
22% with ipilimumab plus nivolumab
Median maximal tumor shrinkage was 54% with ICPI/VEGFR-TKI combinations, compared with 39% with VEGFR-TKI monotherapy and 0% with ipilimumab/nivolumab. No complete responses were observed in the study.
Axitinib plus pembrolizumab extended time to progression
The combination of axitinib and pembrolizumab also showed the longest time to progression. Median time to progression had not been reached in the combination group, compared with 19 months for VEGFR-TKI monotherapy and 27 months for ipilimumab/nivolumab.
When axitinib/pembrolizumab was compared directly with the other first-line approaches combined, time to progression was significantly longer with the combination. The hazard ratio was 0.26 (95% CI, 0.11–0.66; p=0.02).
However, the stronger tumor control did not translate into a demonstrated cancer-specific survival advantage. Cancer-specific survival was similar across the three treatment groups.
Why pancreatic metastases may respond differently
The study also explored the biology of pancreatic metastases. Researchers found higher AXL expression in pancreatic metastases compared with other metastatic sites. They also observed increased infiltration by M2-like anti-inflammatory macrophages and a lower presence of activated CD4+ memory T cells. These characteristics may help explain why pancreatic metastases can be less responsive to immune checkpoint inhibitors alone.
The authors note that the pancreatic metastases in these patients generally displayed an angiogenic and relatively indolent tumor profile, which may contribute to their sensitivity to VEGFR-TKIs.
What the findings mean for treatment
The study does not establish that VEGFR-TKIs should replace current first-line treatment approaches for all patients with metastatic ccRCC. Instead, it provides evidence that VEGFR inhibition appears particularly relevant when pancreatic or thyroid metastases need strong local tumor control.
The authors emphasize that their analysis was retrospective and involved a relatively small number of patients. They also point out that longer follow-up and larger patient groups are needed before survival differences between treatment strategies can be properly assessed.
For patients in whom pancreatic or thyroid metastases threaten to cause problems through local growth or compression, however, the researchers conclude that a VEGFR-TKI should be part of the treatment strategy.
Study publication
The study, “Local control of RCC pancreatic metastases is obtained by angiogenesis inhibitors,” was published online on September 3, 2026, in Acta Clinica Belgica. The research was led by Britt Van Gessel and colleagues.
