医脉通编译，转载请务必注明出处

2016年6月3-7日，一年一度的美国临床肿瘤学会（American Society of Clinical Oncology，ASCO）年会在芝加哥举办。6月4日上午的消化系统（非结直肠）肿瘤壁报专场上，中山大学肿瘤医院肿瘤内科的李宇红教授呈现了一项摘要号为4036的中国研究，该项研究是在转移性食管鳞状细胞癌患者中将rhLTα-Da联合顺铂+氟尿嘧啶，对其疗效和安全性进行评估，医脉通整理如下：

重组人淋巴毒素-α衍生物（rhLTα-Da）是没有N末端27个氨基酸残基的LTα衍生物。之前的研究表明，将rhLTα-Da添加到以顺铂为基础的治疗中是可以耐受的，而且在转移性食管鳞状细胞癌（mESCC）有良好的反应率。这项随机，多中心，对照，IIb期试验是用了评估rhLTα-Da联合顺铂和氟尿嘧啶（PF）作为mESCC一线治疗的疗效和安全性（ChiCTR-TRC-11001197）。

来自中国15个中心的患者随机分为（1:1:1）三组（A组，PF+10μg/m2/d rhLTα-Da；B组，PF+20μg/m2/d rhLTα-Da；C组，单独PF）。主要终点包括无进展生存期（PFS）和确认的总反应率（ORR）。为了评估血清肿瘤坏死因子受体-II（TNFR-II）在预测rhLTα-Da疗效上的作用开展了一项解释性分析。

在2010年9月到2013年5月之间，150例患者入组。在不同组之间基线患者特征相似。在这些组中，没有观察到PFS或ORR的显著性差异。中位PFS在组A是3.9个月（95% 置信区间[CI]：2.9-5.3个月），组B为5.7个月（95% CI：3.2-6.8个月），组C是4.9个月（95% CI：3.1-6.1个月）；ORR分别为：组A是27.1%，组B是46.8%，组C是41.7%（P=0.073）。然而，在低血清TNFR-II水平患者中，组B的中位PFS显著低于其余两组（组B：7.2个月[95% CI：5.1-8.6个月]vs组A：3.5个月[95% CI：1.7-5.5个月；P=0.022]和组C：4.0个月[95% CI：3.2-6.3个月；P=0.027]）。rhLTα-Da添加到PF未显著增加AEs。

虽然主要终点并没有满足，高剂量rhLTα-Da添加到顺铂和氟尿嘧啶方案中可以延长转移性食管鳞状细胞癌低血清TNFR-II水平患者的无进展生存期。未来还需要在已选择的患者中开展进一步的前瞻性研究。临床试验信息：ChiCTR-TRC-11001197。

会议专题》》》2016年ASCO年会专题报道

原文摘要：

Efficacy and safety of rhLTα-Da with cisplatin and fluorouracil in patients with metastatic esophageal squamous cell carcinoma: A randomized, multicenter, open-labelled, controlled, phase IIb trial.（Abstract4036）

Authors：Yu-hong Li, Wenqi Jiang,et al

Session Type：Poster Session

Background: Recombinant human lymphotoxin-α derivative (rhLTα-Da) is the LTα derivative without N-terminal 27 amino acid residues. Our prior studies showed that the addition of rhLTα-Da to cisplatin-based treatment was tolerable and had an encouraging response rate in metastatic esophageal squamous cell carcinoma (mESCC). This randomized, multicenter, controlled, phase II b trial was conducted to evaluate the efficacy and safety of rhLTα-Da with cisplatin and fluorouracil (PF) as the first-line therapy for mESCC (ChiCTR-TRC-11001197). 

Methods: Patients from 15 centers in China were randomly assigned (1:1:1) into three arms (arm A, PF + 10 μg/m2/d rhLTα-Da; arm B, PF + 20 μg/m2/d rhLTα-Da, arm C, PF alone). The primary endpoints included progression-free survival (PFS) and confirmed overall response rate (ORR). An explanatory analysis was performed to evaluate the role of serum tumor necrosis factor receptor-II (TNFR-II) in predicting the efficacy of rhLTα-Da. 

Results: Between September 2010 and May 2013, 150 patients were enrolled. Baseline patients characteristics were similar between arms. No significant difference in either PFS or ORR was observed between these arms. The median PFS was 3.9 months (95% confidence interval [CI]: 2.9-5.3 months) in arm A, 5.7 months (95% CI: 3.2-6.8 months) in arm B, and 4.9 months (95% CI: 3.1-6.1 months) in arm C (P = 0.248); the ORR was 27.1% in arm A, 46.8% in arm B, and 41.7% in arm C (P = 0.073). However, among patients with low levels of serum TNFR-II, the median PFS was significantly longer in arm B than in other two arms (7.2 months [95% CI: 5.1-8.6 months] in arm B vs. 3.5 months [95% CI: 1.7-5.5 months] in arm A [P= 0.022] and 4.0 months [95% CI: 3.2-6.3 months] in arm C [P = 0.027]). The addition of rhLTα-Da to PFdidn't add AEs statistically. 

Conclusions: Although the primary endpoint was not met, the addition of high-dose rhLTα-Da to PF regimen may prolong PFS in mESCC patients with low levels of serum TNFR-II. Further prospective study in selected patients is warranted. Clinical trial information: ChiCTR-TRC-11001197.

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