Tislelizumab plus chemotherapy as first-line treatment for recurrent or metastatic nasopharyngeal cancer: A multicenter phase 3 trial (RATIONALE-309)
Yunpeng Yang, Jianji Pan, Hui Wang, Yuanyuan Zhao, Shenhong Qu, Nianyong Chen, Xiaozhong Chen, Yan Sun, Xiaohui He, Chaosu Hu, Lizhu Lin, Qitao Yu, Siyang Wang, Guihua Wang, Feng Lei, Jiyu Wen, Kunyu Yang, Zhixiong Lin, Ye Guo, Shaoqing Chen, Xiaoming Huang, Yanjie Wu, Liang Liang, Chenqi Chen, Fan Bai, Xiaopeng Ma, Yun Zhang, Shiangjiin Leaw, Li Zhang, Wenfeng Fang
Abstract
Checkpoint inhibitors are effective in recurrent/metastatic nasopharyngeal cancer (R/M NPC). RATIONALE-309 (NCT03924986) randomized 263 treatment-naive R/M NPC patients to tislelizumab or placebo every 3 weeks (Q3W), plus chemotherapy (Q3W for 4-6 cycles). At interim analysis, progression-free survival (PFS) was significantly longer with tislelizumab-chemotherapy versus placebo-chemotherapy (hazard ratio: 0.52; 95% confidence interval: 0.38, 0.73; p < 0.0001). PFS benefit for tislelizumab-chemotherapy versus placebo-chemotherapy was observed regardless of programmed death-ligand 1 expression. PFS after next line of treatment and overall survival showed favorable trends for tislelizumab-chemotherapy versus placebo-chemotherapy. The safety profile was similar between arms. Gene expression profiling (GEP) identified immunologically "hot" tumors, and showed an activated dendritic cell (DC) signature was associated with tislelizumab-chemotherapy PFS benefit. Our results support that tislelizumab-chemotherapy should be considered as first-line treatment for R/M NPC, and GEP and activated DC signature results may help identify patients who might benefit most from immunochemotherapy treatment. VIDEO ABSTRACT.