Efficacy and safety of axitinib in combination with sintilimab as neoadjuvant therapy for patients with locally advanced renal cell carcinoma: A phase II clinical study.

e16534 Background: NCCN, EAU and CUA guidelines recommend radical nephrectomy (RN) for patients with locally advanced renal cell carcinoma (RCC). However, some patients experience complex local invasion, resulting in the difficulty of operation and the high rate of postoperative recurrence. Preoperative neoadjuvant therapy has been shown to reduce tumor volume effectively, consequently increasing the success rate of RN. The objective of this study is to evaluate the effectiveness and safety of combining neoadjuvant Axitinib with sintilimab in these patients. Methods: This is a phase II study to assess the efficacy and safety of neoadjuvant Axitinib combined with sintilimab in RCC patients. Patients diagnosed with locally advanced RCC enrolled in this study received Axitinib (5 mg bid) plus sintilimab (200mg Q3W) until progressive disease or unacceptable toxicity, and then patients will withdraw from the study and explore the option of surgical resection or alternative targeted/immunotherapy. Surgical intervention will be conducted after patients complete four cycles of PD-1 therapy. Results: A total of 12 patients were enrolled in the study. All patients had computerized tomography at screening and after treatment. The median reduction rate of primary tumor volume and active volume in that study were 26.4% and 58.6%, respectively. Stable disease was observed in 10 patients, and partial response was observed in 2 patients and progressive disease was observed in 1 patient. All patients (100.0%) enrolled in the study experienced a treatment-related adverse event (TRAE) of any grade. TRAEs of any grade leading to discontinuation occurred in 2 patients. Only one patient experienced a Grade 3 TRAEs, manifested as increased serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels. Only one patient did not undergo RN due to cardiovascular disease. Conclusions: Most of the patients showed a certain degree of tolerance to the medication and underwent RN successfully. But, only a minority of patients can benefit from Axitinib in Combination with Sintilimab in neoadjuvant therapy for locally advanced RCC. The combination of AKI and PD-1 is still a potential choice for preoperative tumor reduction in locally advanced RCC. There is an urgent need to explore a more effective and safe neoadjuvant therapy for these patients.