Clinical Outcomes and Safety Profile of Neoadjuvant PD-1 Inhibitors Combined With VEGFR-TKI Versus VEGFR-TKI in Nonmetastatic Renal Cell Carcinoma

Cheoklong Ng; Cheng Peng; Shangqian Wang; Lei Zheng; Le Qu; Pei Dong; Changwei Ji; Jun Xiao; Minfeng Chen; Zhankui Jia; Tao Zhang; Xiaoyi Hu; Taile Jing; Wei Xiong; Jianping Wu; Xiongjun Ye; Fan Li; Qing Yang; Qi Tang; Juping Zhao; Xuedong Wei; Jitao Wu; Wen Cai; Guodong Zhu; Zhixian Yu; Zejun Yan; Chancan Li; Zhiyang Huang; Zhenyu Wang; Yonghui Chen; Jin Zhang; Wei Xue; Yige Bao; Chao Qin; Gang Guo; Jiwei Huang

doi:10.1016/j.clgc.2025.102353

Clinical Outcomes and Safety Profile of Neoadjuvant PD-1 Inhibitors Combined With VEGFR-TKI Versus VEGFR-TKI in Nonmetastatic Renal Cell Carcinoma

Clin Genitourin Cancer. 2025 Apr 16:102353. doi: 10.1016/j.clgc.2025.102353. Online ahead of print.

Authors

Cheoklong Ng¹, Cheng Peng², Shangqian Wang³, Lei Zheng⁴, Le Qu⁵, Pei Dong⁶, Changwei Ji⁷, Jun Xiao⁸, Minfeng Chen⁹, Zhankui Jia¹⁰, Tao Zhang¹¹, Xiaoyi Hu¹², Taile Jing¹³, Wei Xiong¹⁴, Jianping Wu¹⁵, Xiongjun Ye¹⁶, Fan Li¹⁷, Qing Yang¹⁸, Qi Tang¹⁹, Juping Zhao²⁰, Xuedong Wei²¹, Jitao Wu²², Wen Cai²³, Guodong Zhu²⁴, Zhixian Yu²⁵, Zejun Yan²⁶, Chancan Li²⁷, Zhiyang Huang²⁸, Zhenyu Wang²⁹, Yonghui Chen¹, Jin Zhang¹, Wei Xue¹, Yige Bao³⁰, Chao Qin³¹, Gang Guo³², Jiwei Huang³³

Affiliations

¹ Department of Urology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
² Department of Urology, The Third Medical Centre, Chinese PLA General Hospital, Beijing, China.
³ Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
⁴ Department of Urology, West China Hospital, Sichuan University, Chengdu 610041, China.
⁵ Department of Urology, Jinling Hospital, Clinical School of Medical College, Nanjing University; Nanjing 210000 China.
⁶ Department of Urology Oncology, Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou 510060, China.
⁷ Department of Urology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing 210008, China.
⁸ Department of Urology, the First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.
⁹ Department of Urology, Xiangya Hospital Central South University, Changsha, Hunan 41008, China.
¹⁰ The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
¹¹ Department of Urology, The Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230601, PR China.
¹² Department of Urology, Zhongshan Hospital, Fudan University, Shanghai, China.
¹³ Department of Urology, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.
¹⁴ Department of Urology, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, Chengdu, China.
¹⁵ Affiliated Zhongda Hospital of Southeast University, Nanjing 210009, China.
¹⁶ Department of Urology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
¹⁷ Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Hubei 430030, PR China.
¹⁸ Department of Urology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China.
¹⁹ Department of Urology, Peking University First Hospital, Peking University, National Urological Cancer Center, Beijing, China.
²⁰ Department of Urology, Ruijin Hospital of Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
²¹ The First Affiliated Hospital of Soochow University, Suzhou 21500, China.
²² Department of Urology, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, Shandong, China.
²³ Department of Urology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China.
²⁴ Department of Urology, the First Affiliated Hospital of Xi'an Jiaotong University. 277 West Yanta Road, Xi'an, PR China.
²⁵ Department of Urology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
²⁶ Department of Urology, the First Affiliated Hospital of Ningbo University, Ningbo 315010,China.
²⁷ Department of Urology, Anhui No.2 Provincial People's Hospital, Hefei, Anhui 230041, China.
²⁸ Department of Urology, Quanzhou First Hospital affiliated to Fujian Medical University, Quanzhou, China.
²⁹ Department of Urology, the Second Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, China.
³⁰ Department of Urology, West China Hospital, Sichuan University, Chengdu 610041, China. Electronic address: baoyige@hotmail.com.
³¹ Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China. Electronic address: qinchao@njmu.edu.cn.
³² Department of Urology, The Third Medical Centre, Chinese PLA General Hospital, Beijing, China. Electronic address: greenguo@sina.com.
³³ Department of Urology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. Electronic address: huangjiwei@renji.com.

PMID: 40348728
DOI: 10.1016/j.clgc.2025.102353

Abstract

Objective: The effectiveness of combining immune checkpoint inhibitors (ICIs) and tyrosine kinase inhibitors (TKIs) in neoadjuvant therapy for renal cell carcinoma (RCC) remains unclear. This study aim to compare the efficacy and safety of neoadjuvant ICI plus TKI combination therapy versus TKI monotherapy in locally RCC patients.

Methods: This study included 185 cases of locally RCC disease(TanyNanyM0) receiving neoadjuvant therapy from 29 centers across China from January 2019 to Feburary 2024. Primary endpoint was the objective response rate (ORR) in all patients and patients with tumor thrombus (TT). Secondary endpoints included recurrence-free survival (RFS), overall survival (OS), surgical outcomes, and safety. Statistical analysis was performed to compare the results between 2 groups.

Results: Combination therapy group had higher ORR compared to the TKI monotherapy group(30.9% vs. 16.3% in all patients, 34.5% vs. 15.6% in patients with TT) and pCR rate (14.8% vs. 0%). RFS rates were improved in patients with TT receiving combination therapy (P = .047). Furthermore, the combination therapy group had lower blood loss during surgery (200 mL vs. 300 mL, P = .004). The main limitation is the retrospective study design.

Conclusions: Neoadjuvant ICI plus TKI combination therapy showed promising efficacy and acceptable toxicity. These findings suggest that further investigation is warranted to explore the potential of this treatment approach.

Keywords: Immune checkpoint inhibitor; Immunotherapy; Neoadjuvant therapy; Targeted therapy; Tumor thrombus.