Lu Zhihao, Zhang Yanqiao, Fan Qingxia, Pan Yueyin, Jiang Da, Lu Ping, Zhang Jingdong, Yuan Xianglin, Feng Jifeng, Yang Shujun, Yue Wenbin, Zhao Lin, Xu Yunhua, Luo Jinhua, Shen Lin
Department of Gastrointestinal Oncology, Peking University Cancer Hospital & Institute, Beijing 100142, China.
Department of Gastrointestinal Medical Oncology, Harbin Medical University Cancer Hospital, Harbin 150081, China.
Innovation (Camb). 2022 Apr 4;3(3):100239. doi: 10.1016/j.xinn.2022.100239. eCollection 2022 May 10.
Lack of effective targeted therapy in metastatic esophageal squamous cell carcinoma (ESCC) underscores the urgent need for identifying new treatment approaches for this challenging disease. We sought to assess the addition of cetuximab to paclitaxel-cisplatin chemotherapy for first-line treatment in patients with metastatic ESCC. In this randomized, multicenter, open-label, phase II clinical trial, patients were randomized to receive paclitaxel-cisplatin (TP) (paclitaxel [175 mg/m intravenously (i.v.) on day 1 of every 3-week cycle] and cisplatin [75 mg/m i.v. on day 1 of every 3-week cycle]) and TP plus cetuximab (CTP) (cetuximab, 400 mg/m i.v. on day 1 of week 1, followed by 250 mg/m weekly), respectively. Targeted next-generation sequencing (NGS) was performed on 89 tumor samples for biomarker exploration. The primary endpoint was progression-free survival (PFS) in the intention-to-treat population. With a median follow-up of 22.6 months, median PFS was 5.7 months (95% confidence interval [CI]: 4.8-7.0) in patients administered CTP versus 4.2 months (95% CI: 3.0-5.3) in the TP group (hazard ratio [HR] = 0.61; 95% CI: 0.40-0.93; p = 0.02). Median overall survival was 11.5 months (95% CI: 7.9-13.1) in the CTP group and 10.5 months (95% CI: 9.0-13.2) in the TP arm (HR = 0.98; 95% CI: 0.67-1.44; p = 0.91). The most common reported greater than or equal to grade 3 adverse events were neutropenia (35.2% versus 22.4%) and leukopenia (25.4% versus 13.2%). In patients with epidermal growth factor receptor (EGFR) amplification tumors (15.7%), PFS was improved with CTP compared with TP treatment (HR = 0.11; 95% CI: 0.01-0.98; p = 0.018). First-line CTP significantly improves PFS, with a manageable safety profile in patients with metastatic ESCC.
转移性食管鳞状细胞癌（ESCC）缺乏有效的靶向治疗方法，这凸显了为这种具有挑战性的疾病寻找新治疗方法的迫切需求。我们试图评估在转移性ESCC患者的一线治疗中，在紫杉醇 - 顺铂化疗基础上加用西妥昔单抗的疗效。在这项随机、多中心、开放标签的II期临床试验中，患者被随机分为接受紫杉醇 - 顺铂（TP）（紫杉醇[每3周周期的第1天静脉注射（i.v.）175mg/m²]和顺铂[每3周周期的第1天静脉注射75mg/m²]）以及TP加西妥昔单抗（CTP）（西妥昔单抗，第1周第1天静脉注射400mg/m²，随后每周静脉注射250mg/m²）两组。对89份肿瘤样本进行了靶向二代测序（NGS）以探索生物标志物。主要终点是意向性治疗人群中的无进展生存期（PFS）。中位随访22.6个月时，接受CTP治疗的患者中位PFS为5.7个月（95%置信区间[CI]：4.8 - 7.0），而TP组为4.2个月（95%CI：3.0 - 5.3）（风险比[HR]=0.61；95%CI：0.40 - 0.93；p = 0.02）。CTP组的中位总生存期为11.5个月（95%CI：7.9 - 13.1），TP组为10.5个月（95%CI：9.0 - 13.2）（HR = 0.98；95%CI：0.67 - 1.44；p = 0.91）。报告的最常见的≥3级不良事件是中性粒细胞减少（35.2%对22.4%）和白细胞减少（25.4%对13.2%）。在表皮生长因子受体（EGFR）扩增肿瘤患者（15.7%）中，与TP治疗相比，CTP治疗可改善PFS（HR = 0.11；95%CI：0.01 - 0.98；p = 0.018）。一线CTP显著改善了转移性ESCC患者的PFS，且安全性可控。
