Neoadjuvant Toripalimab Plus Axitinib for Nonmetastatic Clear Cell Renal Cell Carcinoma With Tumor Thrombus: A Combined Analysis of Two Phase II Clinical Trials

ABSTRACT Neoadjuvant immunotherapy‐based combination holds promises in reducing surgical risk and improving survival for renal cell carcinoma (RCC) with venous tumor thrombus (VTT). However, its role in RCC–VTT has been less explored. To evaluate the efficacy and safety of neoadjuvant toripalimab plus axitinib in nonmetastatic RCC–VTT, we conducted a combined analysis of two Phase II trials with similar design. Thirty‐four patients with nonmetastatic clear cell RCC (ccRCC) and Mayo Level 0–IV VTT were enrolled. Toripalimab plus axitinib was administered for up to 12 weeks before surgery. The primary endpoint was objective response rate (ORR). In this study, the ORR and disease control rates were 41% (14 out of 34) and 97% (33 out of 34), respectively. 47% (16 out of 34) patients experienced a reduction in VTT levels. Grade 3 treatment‐related adverse events (TRAEs) occurred in 24% (eight out of 34) patients, and no Grade 4 or 5 TRAEs were observed. Thirty patients were eligible for surgery, and the surgical strategy was simplified in 53% (16 out of 30) patients. One‐year disease‐free survival and overall survival were 76.7% (95% CI, 59.1–88.2%) and 91.2% (95% CI, 77.0–97.0%), respectively. Multiomics analysis revealed the nonresponder group exhibited significant tumor heterogeneity and a stroma‐characterized tumor microenvironment. In conclusion, neoadjuvant toripalimab plus axitinib was clinically active and safe in patients with nonmetastatic ccRCC–VTT.