Although axitinib has achieved a preferable response rate for advanced renal cell carcinoma (RCC), patient survival remains unsatisfactory. In this study, we evaluated the efficacy and safety of a combination treatment of axitinib and a low dose of pembrolizumab-activated autologous dendritic cells-co-cultured cytokine-induced killer cells in patients with advanced RCC.
All adult patients, including treatment-naive or pretreated with VEGF-targeted agents, were enrolled from May 2016 to March 2019. Patients received axitinib 5 mg twice daily and pembrolizumab-activated dendritic cells-co-cultured cytokine-induced killer cells intravenously weekly for the first four cycles, every 2 weeks for the next four cycles, and every month thereafter.
The 43 patients (22 untreated and 21 previously treated) showed a median progression-free survival (mPFS) of 14.7 months (95% CI, 11.16-18.30). mPFS in treatment-naive patients was 18.2 months, as compared with 14.4 months in pretreated patients (log-rank P-value = 0.07). Overall response rates were 25.6% (95% CI, 13.5-41.2%). Grade 3 or higher adverse events occurred in 5% of patients included hypertension (11.6%) and palmar-plantar erythrodysesthesia (7.0%). Peripheral blood lymphocyte immunophenotype and serum cytokine profile analyses demonstrated increased antitumor immunity after combination treatment particularly in patients with a long-term survival benefit, while those with a minimal survival benefit demonstrated an elevated proportion of peripheral CD8+TIM3+ T cells and lower serum-level immunostimulatory cytokine profile.
The combination therapy was active and well tolerated for treatment of advanced RCC, either as first- or second-line treatment following other targeted agents. Changes in immunophenotype and serum cytokine profile may be used as prognostic biomarkers.
Clinical & translational immunology. 2021 Mar 03*** epublish ***
Meng-Jia Song, Qiu-Zhong Pan, Ya Ding, Jianxiong Zeng, Pei Dong, Jing-Jing Zhao, Yan Tang, Jingjing Li, Zhiling Zhang, Junyi He, Jieying Yang, Yue Huang, Ruiqing Peng, Qi-Jing Wang, Jia-Mei Gu, Jia He, Yong-Qiang Li, Shi-Ping Chen, Rongxing Huang, Zi-Qi Zhou, Chaopin Yang, Yulong Han, Hao Chen, Heping Liu, Shangzhou Xia, Yang Wan, De-Sheng Weng, Liming Xia, Fang-Jian Zhou, Jian-Chuan Xia
Collaborative Innovation Center for Cancer Medicine State Key Laboratory of Oncology in South China Sun Yat-sen University Cancer Center Guangzhou China., Guangzhou Yiyang Bio-technology Co., Ltd Guangzhou China.