Toripalimab Plus Axitinib Shows Promise in Neoadjuvant Treatment of Renal Cell Carcinoma with Vena Cava Thrombus
核心洞察
A neoadjuvant regimen of toripalimab and axitinib demonstrated a significant reduction in tumor thrombus level in patients with clear cell renal cell carcinoma (搜索).
The combination therapy led to a change in surgical approach for 61.9% of patients, often avoiding more invasive procedures like cardiopulmonary bypass.
Progression-free survival at 1 year was 89.1%, and at 2 years was 54.8%, indicating a durable response in a substantial portion of patients.
A combination of toripalimab and axitinib shows promise as a neoadjuvant therapy for clear cell renal cell carcinoma (搜索) (ccRCC) patients with inferior vena cava (搜索) tumor thrombus (IVC-TT). A recent study published in Nature Communications investigated the efficacy and safety of this regimen, revealing significant reductions in thrombus levels and changes in surgical approaches.
The study, a single-center trial, enrolled 25 patients with ccRCC and IVC-TT. Patients received toripalimab, an anti-PD-1 (搜索) antibody, in combination with axitinib, a tyrosine kinase inhibitor (TKI). The primary endpoint was the change in tumor thrombus level after 12 weeks of treatment. Secondary endpoints included overall response rate, progression-free survival, and safety.
Radiological Efficacy and Surgical Impact
The results demonstrated that 44% of patients experienced a reduction in tumor thrombus level. Neoadjuvant therapy significantly reduced the Mayo level of patients with tumor thrombus (Std. MH Statistic = 2.985, P = 0.003). While 56% of patients remained stable in thrombus level, 96% experienced varying degrees of tumor thrombus length reduction. According to RECIST criteria, the best overall tumor response was a partial response in 40% of patients and stable disease in 60%.
Notably, 61.9% of patients experienced changes in their planned surgical strategy. "Four patients with initial level IV TT avoided incision of right atrium and cardiopulmonary bypass, which due to downgrading of Mayo level," the researchers noted. This suggests the neoadjuvant therapy can facilitate less invasive surgical interventions.
Perioperative Outcomes and Safety
Of the 25 patients enrolled, 21 underwent radical nephrectomy with IVC thrombectomy. The median operative time was 314 minutes, and the median estimated blood loss was 800 mL. Postoperative complications occurred in 57.1% of patients, with transient renal dysfunction and the need for postoperative transfusion being the most common minor complications. There was a 4.8% mortality rate, with one patient dying of hemorrhagic shock during surgery.
Treatment-related adverse events (TRAEs) occurred in all patients, but most were grade 1 or 2. Grade 3 TRAEs were observed in 28% of patients, with hypertension and proteinuria being the most common. Discontinuation of toripalimab occurred in two patients, and axitinib was discontinued in another two due to adverse events.
Survival and Translational Analysis
The median follow-up time was 23.3 months. The median progression-free survival (PFS) was 25.3 months. The 1-year and 2-year PFS rates were 89.1% and 54.8%, respectively. Translational analyses of pre-operative tumor samples revealed higher levels of T cytotoxic cells in non-responders, but these cells were predominantly PD-1 (搜索) positive, contributing to an immunosuppressive tumor microenvironment. scRNA-seq analysis of post-treatment samples showed differences in cell composition between responders and non-responders, particularly in T cell subsets.
Implications
These findings suggest that neoadjuvant toripalimab in combination with axitinib is a promising treatment strategy for patients with ccRCC and IVC-TT. The therapy demonstrated significant radiological responses, facilitated less invasive surgical approaches, and showed encouraging progression-free survival. Further research is needed to validate these findings in larger, multi-center trials and to identify predictive biomarkers for treatment response.