特瑞普利单抗联合化疗治疗先前未经治疗的晚期NSCLC患者：一项多中心随机 III 期试验 (CHOICE-01)

SCI

23 Octember 2022

Toripalimab Plus Chemotherapy for Patients With Treatment-Naive Advanced Non– Small-Cell Lung Cancer: A Multicenter Randomized Phase III Trial (CHOICE-01)

 (IF: JCO., 50.717)

Wang Z, Wu L, Li B, Cheng Y, Li X, Wang X, Han L, Wu X, Fan Y, Yu Y, Lv D, Shi J, Huang J, Zhou S, Han B, Sun G, Guo Q, Ji Y, Zhu X, Hu S, Zhang W, Wang Q, Jia Y, Wang Z, Song Y, Wu J, Shi M, Li X, Han Z, Liu Y, Yu Z, Liu AW, Wang X, Zhou C, Zhong D, Miao L, Zhang Z, Zhao H, Yang J, Wang D, Wang Y, Li Q, Zhang X, Ji M, Yang Z, Cui J, Gao B, Wang B, Liu H, Nie L, He M, Jin S, Gu W, Shu Y, Zhou T, Feng J, Yang X, Huang C, Zhu B, Yao Y, Tang X, Yu J, Maher E, Feng H, Yao S, Keegan P, Wang J. Toripalimab Plus Chemotherapy for Patients With Treatment-Naive Advanced Non-Small-Cell Lung Cancer: A Multicenter Randomized Phase III Trial (CHOICE-01). J Clin Oncol. 2022 Oct 7:JCO2200727. 

CORRESPONDING AUTHOR Jie Wang, MD, State Key Laboratory of Molecular Oncology, Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China; e-mail: zlhuxi@163.com.

PURPOSE 目的

The CHOICE-01 study investigated the efficacy and safety of toripalimab in combination with chemotherapy as a first-line treatment for advanced non–small-cell lung cancer (NSCLC). 

CHOICE-01研究调查了特瑞普利单抗联合化疗作为晚期非小细胞肺癌 (NSCLC) 一线治疗的疗效和安全性。

PATIENTS AND METHODS 患者与方法

Patients (N=465) with treatment-naive, advanced NSCLC without EGFR/ALK mutations were randomly assigned 2:1 to receive toripalimab 240 mg (n=309) or placebo (n=156) once every 3 weeks in combination with chemotherapy for 4-6 cycles, followed by the maintenance of toripalimab or placebo once every 3 weeks plus standard care. Stratification factors included programmed death ligand-1 expression status, histology, and smoking status. The primary end point was progression-free survival (PFS) by investigator per RECIST v1.1. Secondary end points included overall survival and safety. 

先前未接受过治疗、无EGFR/ALK 突变的晚期 NSCLC 患者（N=465）被随机以 2:1分配，接受每 3 周一次的特瑞普利单抗240 mg（n=309）或安慰剂（n=156）治疗，并联合化疗 4-6 个周期，随后每 3 周维持一次特瑞普利单抗或安慰剂加标准治疗。分层因素包括程序性死亡配体-1表达状态、组织学和吸烟状态。主要终点是研究者根据RECIST v1.1确定的无进展生存期 (PFS)。次要终点包括总生存期和安全性。

RESULTS 结果

At the final PFS analysis, PFS was significantly longer in the toripalimab arm than in the placebo arm (median PFS 8.4 v 5.6 months, hazard ratio=0.49; 95% CI, 0.39 to 0.61; two-sided P< .0001). At the interim OS analysis, the toripalimab arm had a significantly longer OS than the placebo arm (median OS not reached v 17.1 months, hazard ratio=0.69; 95% CI, 0.53 to 0.92; two-sided P=.0099). The incidence of grade ≥ 3 adverse events was similar between the two arms. Treatment effects were similar regardless of programmed death ligand-1 status. Genomic analysis using whole-exome sequencing from 394 available tumor samples revealed that patients with high tumor mutational burden were associated with significantly better PFS in the toripalimab arm (median PFS 13.1 v 5.5 months, interaction P=.026). Notably, patients with mutations in the focal adhesion-PI3K-Akt signaling pathway achieved significantly better PFS and OS in the toripalimab arm (interaction P values≤.001).

在最终的PFS分析中，特瑞普利单抗组的PFS明显长于安慰剂组（中位PFS 8.4 vs 5.6个月，风险比= 0.49；95% CI，0.39至0.61；双侧P<.0001）。在中期OS分析中，特瑞普利单抗组的OS显著长于安慰剂组（中位OS未达到vs 17.1个月，风险比=0.69；95% CI，0.53至0.92；双侧 P=0.0099）。两组之间≥3级不良事件的发生率相似。无论程序性死亡配体-1状态如何，治疗效果都相似。使用来自394个可用肿瘤样本的全外显子组测序进行的基因组分析显示，高肿瘤突变负荷患者与特瑞普利单抗组的PFS显著改善相关（中位PFS 13.1 vs 5.5个月，相互作用P=0.026）。值得注意的是，局部粘连-PI3K-Akt信号通路突变的患者在特瑞普利单抗组中获得了显著更好的PFS和OS获益（相互作用P值≤.001).

CONCLUSION 结论

Toripalimab plus chemotherapy significantly improves PFS and OS in patients with treatment-naive advanced NSCLC while having a manageable safety profile. Subgroup analysis showed the OS benefit was mainly driven by the nonsquamous subpopulation.

特瑞普利单抗联合化疗可显著改善未经治疗的晚期NSCLC患者的PFS和OS，同时具有可控的安全性。亚组分析显示，OS获益主要由非鳞状亚群驱动。

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