Acta clinica Belgica · 2026
Local control of RCC pancreatic metastases is obtained by angiogenesis inhibitors.
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Van Gessel Britt, Kinget Lisa, Mammone Giulia, Zarba Martin, Albersen Maarten, Debruyne Philip R, Baldewijns Marcella, Biesemans Pauline, Van Den Bulck Heidi, Dumez Herlinde, Demeulenaere Octavie, Topal Baki, Topal Halit, Vandermeulen Henri, Garg Abhishek D, Laenen Annouschka, McTaggart Edward Scott, Naulaerts Stefan, Heng Daniel, Beuselinck Benoit
Аннотация
BACKGROUND: Metastatic clear-cell renal cell carcinoma (m-ccRCC) with pancreatic and/or thyroid metastases (PM/TM) is sensitive to vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKIs). Optimal first-line therapy for these patients (VEGFR-TKI-monotherapy, immune checkpoint inhibitor (ICPI) combinations (ipilimumab/nivolumab) or ICPI/VEGFR-TKI-combinations) remains unknown.
MATERIALS AND METHODS: We studied (A) the specific impact of axitinib and/or pembrolizumab dose reductions and treatment interruptions on response in patients treated with axitinib/pembrolizumab, (B) tumor shrinkage in individual PM upon VEGFR-TKIs and ICPIs, (C) the optimal first-line therapy in m-ccRCC patients with PM/TM in terms of tumor shrinkage, response rate (RR), time-to-progression (TTP) and cancer-specific-survival (CSS) and (D) explored molecular features of PM.
RESULTS: We describe 5 cases of m-ccRCC patients with PM, treated with first-line axitinib/pembrolizumab, in whom tumor response was clearly linked to axitinib administration and dose rather than pembrolizumab. In 119 individual PM, tumor shrinkage was the highest with ICPI/VEGFR-TKI-combinations followed by VEGFR-TKIs-monotherapy and lowest with ICPIs without VEGFR-TKIs (p < 0.0001). In 40 patients with PM/TM, median maximal tumor shrinkage was -54%, -39% and 0%, respectively (p = 0.04). RR was 83% with ICPI/VEGFR-TKI-combinations, 69% with VEGFR-TKI-monotherapy and 22% with ipilimumab/nivolumab (p = 0.01). Median TTP was not reached, 19 and 27 months, respectively (p = 0.07). Median CSS was not similarly impacted by first-line therapy. PM displayed high AXL-expression and higher infiltration by M2-like anti-inflammatory macrophages compared to other metastatic sites.
CONCLUSION: In m-ccRCC patients with PM/TM, first-line therapy with VEGFR-TKIs or ICPI/VEGFR-TKI-combinations leads to improved RR and tumor shrinkage, compared to ipilimumab/nivolumab, but not to CSS benefit in the current analysis. PM displayed high AXL-expression and higher infiltration by M2-like anti-inflammatory macrophages compared to other metastatic sites.
MATERIALS AND METHODS: We studied (A) the specific impact of axitinib and/or pembrolizumab dose reductions and treatment interruptions on response in patients treated with axitinib/pembrolizumab, (B) tumor shrinkage in individual PM upon VEGFR-TKIs and ICPIs, (C) the optimal first-line therapy in m-ccRCC patients with PM/TM in terms of tumor shrinkage, response rate (RR), time-to-progression (TTP) and cancer-specific-survival (CSS) and (D) explored molecular features of PM.
RESULTS: We describe 5 cases of m-ccRCC patients with PM, treated with first-line axitinib/pembrolizumab, in whom tumor response was clearly linked to axitinib administration and dose rather than pembrolizumab. In 119 individual PM, tumor shrinkage was the highest with ICPI/VEGFR-TKI-combinations followed by VEGFR-TKIs-monotherapy and lowest with ICPIs without VEGFR-TKIs (p < 0.0001). In 40 patients with PM/TM, median maximal tumor shrinkage was -54%, -39% and 0%, respectively (p = 0.04). RR was 83% with ICPI/VEGFR-TKI-combinations, 69% with VEGFR-TKI-monotherapy and 22% with ipilimumab/nivolumab (p = 0.01). Median TTP was not reached, 19 and 27 months, respectively (p = 0.07). Median CSS was not similarly impacted by first-line therapy. PM displayed high AXL-expression and higher infiltration by M2-like anti-inflammatory macrophages compared to other metastatic sites.
CONCLUSION: In m-ccRCC patients with PM/TM, first-line therapy with VEGFR-TKIs or ICPI/VEGFR-TKI-combinations leads to improved RR and tumor shrinkage, compared to ipilimumab/nivolumab, but not to CSS benefit in the current analysis. PM displayed high AXL-expression and higher infiltration by M2-like anti-inflammatory macrophages compared to other metastatic sites.