Radical nephrectomy with inferior vena cava (IVC) thrombectomy was associated with high surgical morbidity and mortality. Preoperative tumor thrombus (TT) downgrading may reduce surgical coverage and surgical complications. After neoadjuvant targeted therapy, the reduction rate of thrombus level was limited.
Methods
NEOTAX was a single-arm, interventional, phase 2 study of neoadjuvant toripalimab in combination with axitinib in patients with clear cell renal cell carcinoma (ccRCC) and IVC-TT (Mayo level Ⅱ–Ⅳ). Toripalimab was administered at 240 mg every 3 weeks, lasted up to 4 cycles. The dose of axitinib was 5 mg BID. The primary endpoint was the down-staging rate of IVC-TT level. Secondary endpoints were percentage change in surgical approach and TT length, response rate (RECISTv1.1), progression-free survival, surgical morbidity, and biomarker exploration.
Results
In all, 25 patients received study treatment, 44% (11/25) patients experienced a reduction in thrombus level, and none experienced an increase in Mayo level. Neoadjuvant therapy significantly reduced the Mayo level of patients with tumor thrombus (P < 0.001). The median change in tumor thrombus length was -2.3 cm (range: -7.1 to 1.1 cm). Overall, 61.9% (13/21) patients experienced changes in surgical strategy compared with planned surgery, 3 patients experienced major complications. The 1-year progression-free survival was 89.1% (95% CI: 62.7-97.2). There were no grade 4/5 treatment-related adverse events. Overall, grade 3 AEs occurred in seven patients (28%). The most common grade 3 TRAEs were hypertension (8%), and proteinuria (8%). Biopsy samples of non-responders exhibited increased T cytotoxic cell infiltration, but these cells were predominantly PD-1 positive. Biopsy samples of responders exhibited lower T helper cells, however, their subtype, regulatory T cells remained unchanged. In surgical samples of the TT, non-responders exhibited increased CD8T_01_GZMK_CXCR4 subset T cells.
Conclusions
NEOTAX provides the first level II evidence that toripalimab in combination with axitinib downstages IVC-TT in a significant proportion of patients leading to reduction in the extent of surgery.
Clinical trial identification
ChiCTR2000030405.