Tislelizumab Combined With Induction Chemotherapy and Concurrent Chemoradiotherapy in Locally Advanced Esophageal Squamous Cell Carcinoma: A Multicenter, Randomized, Phase II Trial (EC-CRT-002).

Methods

This multicenter, randomized, open-label, phase II trial was conducted across four academic hospitals in China (ClinicalTrials.gov identifier: NCT05520619).

这项多中心、随机、开放标签的II期临床试验在中国四家学术医院进行（ClinicalTrials.gov注册号：NCT05520619）。

Participants were adults age 18-70 years with newly diagnosed, unresectable, stage II to IVB ESCC.

参与者为年龄在18-70岁之间的成人，患有新诊断的、无法手术切除的、II至IVB期食管鳞癌。

Patients were randomly assigned (1:1) to receive two cycles of paclitaxel/cisplatin induction chemotherapy followed by concurrent CRT in combination with tislelizumab for 16 cycles in group A (two induction, two concurrent, and 12 maintenance) or four cycles in group B (two induction and two concurrent).

患者按1:1的比例随机分配，接受两周期紫杉醇/顺铂诱导化疗，随后在A组接受16周期的同步放化疗联合替雷利珠单抗治疗（两周期诱导，两周期同步，和12周期维持），或在B组接受四周期治疗（两周期诱导和两周期同步）。

The primary end point was progression-free survival(PFS) in the intention-to-treatpopulation, compared with historical control.

主要终点是意向治疗人群中无进展生存期（PFS），与历史对照组进行比较。

Results

Between October 2022 and October 2024, 114 patients were randomly assigned to group A (n = 57) or group B (n = 57).

在2022年10月至2024年10月期间，共有114名患者被随机分配到A组（n = 57）或B组（n = 57）。

After a median follow-up of 22.7 months (IQR, 16.2-28.2), group B demonstrated significantly better PFS versus controls (1-year: 71.9% [95% CI, 61.1 to 84.6] v 56.4% [95% CI, 44.7 to 71.1]; hazard ratio[HR], 0.54 [95% CI, 0.32 to 0.94]), while group A showed no PFS benefit (1-year: 52.6% [95% CI, 41.4 to 67.3]; HR, 1.06 [95% CI, 0.67 to 1.68]).

中位随访时间为22.7个月（四分位数间距，16.2-28.2），与对照组相比，B组显示出显著更好的无进展生存（PFS）（1年：71.9% [95% 置信区间, 61.1到84.6] 对比 56.4% [95% 置信区间, 44.7到71.1]；风险比[HR]，0.54 [95% 置信区间, 0.32到0.94]），而A组未显示出PFS获益（1年：52.6% [95% 置信区间, 41.4到67.3]；HR，1.06 [95% 置信区间, 0.67到1.68]）。

Overall survivalwas also significantly better in group B (HR, 0.42 [95% CI, 0.22 to 0.82]).

B组的总生存（OS）也显著更好（HR, 0.42 [95% 置信区间, 0.22到0.82]）。

Grade ≥3 adverse events occurred in 86.0% of group A and 80.7% of group B, with the most common being lymphopenia (77.2% and 73.7%, respectively).

在A组和B组中，3级或更高级别的不良事件发生率分别为86.0%和80.7%，其中最常见的为淋巴细胞减少症（分别为77.2%和73.7%）。

Comprehensive biomarker analyses revealed that PD-L1 expression, CD8+ T-cell density, NRF2 pathway mutations, and dynamic changes in circulating tumor DNA were associated with treatment efficacy.

全面的生物标志物分析显示，PD-L1表达、CD8+ T细胞密度、NRF2通路突变以及循环肿瘤DNA的动态变化与治疗效果相关。

Conclusions

The addition of tislelizumab to induction chemotherapy and concurrent CRT without maintenance immunotherapy demonstrated superior efficacy and manageable toxicity in locally advanced ESCC.

在局部晚期食管鳞癌中，将替雷利珠单抗加入诱导化疗和同步放化疗中，而不进行维持免疫治疗，显示出优越的疗效和可控的毒性。