Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Department of Gastrointestinal Oncology, Cancer Center, Fifth Medical Center General Hospital of PLA, Beijing, China.
Lancet Oncol. 2020 Jun;21(6):832-842. doi: 10.1016/S1470-2045(20)30110-8. Epub 2020 May 13.
Patients with advanced or metastatic oesophageal squamous cell carcinoma have poor prognosis and few treatment options after first-line therapy. We aimed to assess efficacy and safety of the anti-PD-1 antibody camrelizumab versus investigator's choice of chemotherapy in previously treated patients.
ESCORT is a randomised, open-label, phase 3 study of patients aged 18 to 75 years with a histological or cytological diagnosis of advanced or metastatic oesophageal squamous cell carcinoma done at 43 hospitals in China. Eligible patients had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, and had progressed on, or were intolerant to, first-line standard therapy. Patients were randomly assigned (1:1) to camrelizumab (200 mg every 2 weeks) or chemotherapy with docetaxel (75 mg/m every 3 weeks) or irinotecan (180 mg/m every 2 weeks), all given intravenously. Central randomisation was done using the Randomization and Trial Supply Management system with block size randomly generated as four or six and stratified by disease and ECOG performance status. The primary endpoint was overall survival, assessed in randomised patients who had received at least one dose of treatment. Safety was assessed in all treated patients. The trial is registered with ClinicalTrials.gov, NCT03099382, and is closed to new participants.
From May 10, 2017, to July 24, 2018, 457 (75%) of 607 screened patients were randomly assigned to treatment, of whom 228 received camrelizumab treatment and 220 received chemotherapy. As of data cutoff on May 6, 2019, with a median follow-up time of 8·3 months (IQR 4·1-12·8) in the camrelizumab group and 6·2 months (3·6-10·1) in the chemotherapy group, median overall survival was 8·3 months (95% CI 6·8-9·7) in the camrelizumab group and 6·2 months (5·7-6·9) in the chemotherapy group (hazard ratio 0·71 [95% CI 0·57-0·87]; two-sided p=0·0010). The most common treatment-related adverse events of grade 3 or worse were anaemia (camrelizumab vs chemotherapy: six [3%] vs 11 [5%]), abnormal hepatic function (four [2%] vs one [<1%]), and diarrhoea (three [1%] vs nine [4%]). Serious treatment-related adverse events occurred in 37 (16%) of 228 patients in the camrelizumab group, and in 32 (15%) of 220 patients in the chemotherapy group. Ten treatment-related deaths occurred, seven (3%) in the camrelizumab group (three deaths from unknown causes, one enterocolitis, one hepatic function abnormal, one pneumonitis, and one myocarditis) and three (1%) in the chemotherapy group (two deaths from unknown causes, and one gastrointestinal haemorrhage).
Second-line camrelizumab significantly improved overall survival in patients with advanced or metastatic oesophageal squamous cell carcinoma compared with chemotherapy, with a manageable safety profile. It might represent a potential option of standard second-line treatment for patients with oesophageal squamous cell carcinoma in China.
Jiangsu Hengrui Medicine.
一线治疗后，晚期或转移性食管鳞癌患者预后较差，治疗选择有限。我们旨在评估抗 PD-1 抗体卡瑞利珠单抗与研究者选择的化疗在先前治疗的患者中的疗效和安全性。
ESCORT 是一项在中国 43 家医院进行的随机、开放标签、III 期研究，纳入年龄在 18 至 75 岁之间、组织学或细胞学诊断为晚期或转移性食管鳞癌的患者。入组患者的东部肿瘤协作组（ECOG）体能状态为 0 或 1，在接受一线标准治疗后进展或不耐受。患者按 1:1 随机分配至卡瑞利珠单抗（每 2 周 200mg）或多西他赛（每 3 周 75mg/m2）或伊立替康（每 2 周 180mg/m2）化疗，均为静脉输注。采用随机化和试验供应管理系统进行中心随机化，采用随机生成的四或六单位分组大小，并按疾病和 ECOG 体能状态分层。主要终点是随机入组的接受至少一剂治疗的患者的总生存期。所有治疗患者的安全性均进行评估。该试验在 ClinicalTrials.gov 注册，NCT03099382，现已关闭入组。
自 2017 年 5 月 10 日至 2018 年 7 月 24 日，共筛选出 607 例患者，其中 457 例（75%）患者随机分配治疗，其中 228 例接受卡瑞利珠单抗治疗，220 例接受化疗。截至 2019 年 5 月 6 日数据截止时，卡瑞利珠单抗组中位随访时间为 8.3 个月（IQR 4.1-12.8），化疗组为 6.2 个月（3.6-10.1），卡瑞利珠单抗组中位总生存期为 8.3 个月（95%CI 6.8-9.7），化疗组为 6.2 个月（5.7-6.9）（风险比 0.71[95%CI 0.57-0.87]；双侧 p=0.0010）。最常见的 3 级或更高级别的治疗相关不良事件为贫血（卡瑞利珠单抗 vs 化疗：6[3%] vs 11[5%]）、肝功能异常（4[2%] vs 1[<1%]）和腹泻（3[1%] vs 9[4%]）。卡瑞利珠单抗组 228 例患者中有 37 例（16%）发生严重治疗相关不良事件，化疗组 220 例患者中有 32 例（15%）发生严重治疗相关不良事件。卡瑞利珠单抗组有 10 例治疗相关死亡，7 例（3%）死因不明，1 例为肠炎，1 例为肝功能异常，1 例为肺炎，1 例为心肌炎；化疗组有 3 例（1%）治疗相关死亡，2 例死因不明，1 例为胃肠道出血。
二线卡瑞利珠单抗治疗晚期或转移性食管鳞癌患者显著改善了总生存期，安全性可控。它可能是中国食管鳞癌患者二线标准治疗的潜在选择。
江苏恒瑞医药。
