1. Tislelizumab plus chemotherapy as first-line treatment for recurrent or metastatic nasopharyngeal cancer: A multicenter phase 3 trial (RATIONALE-309).
- Author
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Yang, Yunpeng, Pan, Jianji, Wang, Hui, Zhao, Yuanyuan, Qu, Shenhong, Chen, Nianyong, Chen, Xiaozhong, Sun, Yan, He, Xiaohui, Hu, Chaosu, Lin, Lizhu, Yu, Qitao, Wang, Siyang, Wang, Guihua, Lei, Feng, Wen, Jiyu, Yang, Kunyu, Lin, Zhixiong, Guo, Ye, and Chen, Shaoqing
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PROGRAMMED cell death 1 receptors , *CLINICAL trials , *NASOPHARYNX cancer , *PROGRAMMED death-ligand 1 , *GENE expression profiling , *METASTASIS , *CISPLATIN - 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. [Display omitted] [Display omitted] • First-line tislelizumab plus chemotherapy improves PFS, PFS2, and OS • The combination shows a manageable safety profile in patients with R/M NPC • Efficacy is observed irrespective of EBV level and PD-L1 expression • Patients with high levels of activated dendritic cell signature may benefit most from treatment Yang et al. demonstrate the efficacy and safety of tislelizumab plus chemotherapy (gemcitabine-cisplatin) in treatment-naive patients with recurrent/metastatic nasopharyngeal cancer. Compared with placebo-chemotherapy, tislelizumab-chemotherapy extends progression-free survival, irrespective of PD-L1 expression, as well as progression-free survival after next line of treatment, with a tolerable safety profile. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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