Association of radiographic and pathologic outcomes in patients (pts) with advanced renal cell carcinoma (RCC) with and without thrombus receiving preoperative immune checkpoint inhibitor (ICI) regimens and circulating biomarkers

Background: Primary RCC tumors and associated IVC thrombus have similar histology, however response to ICI is not always concordant. RCC with IVC thrombus is often difficult to manage, and perioperative ICI treatment responses remain largely unstudied. Methods: We conducted a retrospective analysis of pts with advanced RCC receiving preoperative ICI-based regimens at UTSW stratified by the presence of tumor thrombus. The primary objectives were pathologic change in both groups and radiographical response by RECIST 1.1 criteria for tumor and thrombus level change. The secondary objective was to evaluate biomarkers associated with thrombus. Comparisons were performed using a two-sample t-test or aChi-square test. Results: 65 pts were included (median age 64 years), 31 (48%) with baseline thrombus (9 (29%) renal vein thrombus; 6 (19%) level 1 IVC thrombus; 10 (32%) level 2; 2 (7%) level 3; and 4 (13%) level 4). 28 pts (43%) received ICI+ICI, while 20 pts (31%) received ICI+TKI and the rest received ICI monotherapy. 18/31 pts (58%) with thrombus and 20/34 without thrombus (59%) had metastasis at baseline. Pathological Tumor (pT) downstaging occurred in 13 pts with and 11 pts without thrombus; of these, 12 pts had received ICI+TKI and 12 pts ICI+ICI. Radiographic tumor (cT) downstaging occurred in 8/31 pts with thrombus and 7/34 pts without. 12/31 pts experienced thrombus downstaging. 5 pts with thrombus vs 2 pts without had complete tumor necrosis/pCR in the primary and radiographic PR, of whom 4/7 received ICI+TKI. In pts with IVC thrombus, preoperative ICI based regimens reduced median tumor size from 9.1 to 7.7 cm. Among responders in pts with IVC thrombus, ICI+TKI had a trend toward higher tumor shrinkage median (-3.3 vs -1.9 cm, p=0.3) and thrombus downstaging median (-2 vs -1 levels, p=0.27) than ICI+ICI. Baseline anemia (Hemoglobin (Hgb), 11.1 vs 13.1 g/dL, p=0.002), lower Absolute Lymphocyte Count (ALC) (1.35x10^3 vs 1.55 x10^3 cells/uL, p=0.03), and higher Neutrophil-to-Lymphocyte ratio (NLR) (3.6 vs 3.2, p=0.03) were observed in pts with IVC thrombus. Conclusions: ICI+TKI regimens tend to have tumor downstaging, complete tumor necrosis/pCR in primary tumors, and some IVC thrombus control compared to ICI+ICI regimens. IVC thrombus is associated with lower Hgb and ALC and higher NLR levels. Prospective trials are ongoing to investigate perioperative treatment in pts with IVC thrombus. Research Sponsor: None.

Duke Scholars

Author Tian Zhang Medicine, Medical Oncology