背景:不可切除的局部晚期食管鳞状细胞癌(ESCC)患者的标准治疗是使用5-FU加顺铂的确定性放化疗(CRT)。然而,完全反应(CR)率很低,为11-25%,导致9-10个月的中位总生存期(OS)。据报道,在局部晚期非小细胞肺癌患者中,通过将免疫疗法与放射疗法结合可以提高治疗效果。使用ESCC细胞系的结果表明,在CRT完成后不久用抗PD-L1药物进行序贯治疗是最有效的组合。
方法:TENERGY试验是一个多中心,第二阶段,概念验证研究旨在评估阿特珠单抗在局部晚期ESCC患者行最终CRT后的疗效和安全性.主要纳入标准是不可切除的局部晚期ESCC,无远处转移,完成60Gy的放疗加两个伴随的化疗周期(顺铂70mg/m2在第1天和5-FU700mg/m2在第1-4天,每28天),和适当的器官功能。CRT后6周内,参与者将开始每3周服用1200mg阿妥珠单抗,并持续至12个月或疾病进展.主要终点是研究者评估确认的CR率。次要终点包括总体反应率,无进展生存期(PFS),操作系统,不良事件,并通过中央评估确认CR率。我们将招募50例患者(40例原发性局部晚期ESCC和10例术后局部复发性ESCC)。我们将从原发部位获得活检,并在3个时间点收集血液(CRT前,在CRT之后,和阿特珠单抗开始后四周)进行探索性生物标志物研究。我们将分析免疫活性细胞的表型,新抗原,肿瘤突变负担,PD-L1状态,和人类白细胞抗原单体分型。
结论:CRT和阿替珠单抗序贯联合应用的协同作用可提高CR率,导致无法切除的局部晚期ESCC患者的生存改善。因为CRT是早期到局部晚期ESCC患者的标准治疗选择,CRT和阿替珠单抗的序贯组合有可能改变标准ESCC治疗方法.
背景:UMIN000034373,10/04/2018和EPOC1802。
BACKGROUND: The standard treatment for patients with unresectable locally advanced esophageal squamous cell carcinoma (ESCC) is definitive chemoradiotherapy (CRT) using 5-FU plus cisplatin. However, complete response (CR) rates are low at 11-25%, resulting in 9-10 months of median overall survival (OS). An improved therapeutic efficacy by combining immunotherapy with radiation has been reported in patients with locally advanced non-small cell lung cancer. The results using ESCC cell lines suggest sequential treatment with anti-PD-L1 agents soon after completion of CRT is the most effective combination.
METHODS: TENERGY trial is a multicenter, phase II, proof-of-concept study to assess the efficacy and safety of atezolizumab following definitive CRT in patients with locally advanced ESCC. The main inclusion criteria are unresectable locally advanced ESCC without distant metastasis, completion of 60 Gy of radiation plus two concomitant cycles of chemotherapy (cisplatin 70 mg/m2 on day 1 and 5-FU 700 mg/m2 on days 1-4, every 28 days), and adequate organ function. Within 6 weeks after CRT, participants will start taking 1200 mg of atezolizumab every three weeks and continue until 12 months or disease progression. The primary endpoint is the confirmed CR rate by the investigator\'s assessment. Secondary endpoints include overall response rate, progression-free survival (PFS), OS, adverse events, and confirmed CR rate by central assessment. We will enroll 50 patients (40 with primary locally advanced ESCC and 10 with postoperative locoregionally recurrent ESCC). We will obtain biopsies from the primary site and will collect blood at 3 time points (before CRT, after CRT, and four weeks after the start of atezolizumab) for an exploratory biomarker study. We will analyze the phenotype of immune-competent cells, neoantigens, tumor mutational burden, PD-L1 status, and Human Leukocyte Antigen haplotyping.
CONCLUSIONS: The synergistic efficacies of the sequential combination of CRT and atezolizumab should improve the CR rate, resulting in survival improvement for patients with unresectable locally advanced ESCC. Because CRT is a standard treatment option for patients with early stage to locally advanced ESCC, the sequential combination of CRT and atezolizumab has the potential to change the standard ESCC treatments.
BACKGROUND: UMIN000034373, 10/04/2018 and EPOC1802.