Bai Ming, Wang Meng, Deng Ting, Bai Yuxian, Zang Kai, Miao Zhanhui, Gai Wenlin, Xie Liangzhi, Ba Yi
Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, China.
Department of Gastrointestinal Oncology, Harbin Medical University Cancer Hospital, Harbin 150081, China.
Cancer Biol Med. 2022 Jan 12;19(3):358-69. doi: 10.20892/j.issn.2095-3941.2021.0388.
The mainstay treatment of esophageal squamous cell carcinoma (ESCC) involves chemotherapy and immunotherapy. However, alternative therapies are required for patients who are refractory or intolerant to existing therapies.
In this single-arm, multicenter, open-label phase Ib study, 30 patients received an intravenous infusion of SCT200, an antiepidermal growth factor receptor (EGFR) monoclonal antibody, 6.0 mg/kg once a week for 6 weeks, followed by 8.0 mg/kg once every 2 weeks until disease progression or intolerable toxicity. The primary endpoint was the objective response rate (ORR). The secondary endpoints were progression-free survival (PFS), overall survival (OS), and safety.
Thirty patients were enrolled between July 2018 and May 2019. The ORR was 16.7% (95% CI: 5.6%-34.7%). The median PFS and OS were 3.1 months (95% CI: 1.5-4.3) and 6.8 months (95% CI: 4.7-10.1), respectively. A numerical difference without any statistical significance in ORR was observed in patients with different EGFR expressions (≥ 50%: 25.0% < 50%: 0%, = 0.140) or TP53 mutation abundance (< 10%: 23.8% ≥ 10%: 0%, = 0.286). Improved median PFS (3.4 1.4 months, = 0.006) and OS (8.0 4.2 months, = 0.027) were associated with TP53 mutation abundance of < 10%. The most common treatment-related adverse events of grade 3 or 4 (occurring in ≥ 2 patients) were hypomagnesemia [7 (23.3%)] and rash [2 (6.7%)]. No treatment-related death occurred.
SCT200 monotherapy as the second- or further-line treatment for advanced ESCC showed favorable efficacy, with an acceptable safety profile. TP53 mutation abundance might serve as a potential predictive biomarker.
食管鳞状细胞癌（ESCC）的主要治疗方法包括化疗和免疫治疗。然而，对于对现有治疗难治或不耐受的患者，需要替代疗法。
在这项单臂、多中心、开放标签的Ib期研究中，30例患者接受静脉输注SCT200（一种抗表皮生长因子受体（EGFR）单克隆抗体），6.0mg/kg，每周1次，共6周，随后8.0mg/kg，每2周1次，直至疾病进展或出现不可耐受的毒性。主要终点是客观缓解率（ORR）。次要终点是无进展生存期（PFS）、总生存期（OS）和安全性。
2018年7月至2019年5月共纳入30例患者。ORR为16.7%（95%CI：5.6%-34.7%）。中位PFS和OS分别为3.1个月（95%CI：1.5-4.3）和6.8个月（95%CI：4.7-10.1）。在不同EGFR表达（≥50%：25.0%；<50%：0%，P=0.140）或TP53突变丰度（<10%：23.8%；≥10%：0%，P=0.286）的患者中，ORR存在数值差异，但无统计学意义。TP53突变丰度<10%与中位PFS（3.4对1.4个月，P=0.006）和OS（8.0对4.2个月，P=0.027）改善相关。最常见的3级或4级治疗相关不良事件（≥2例患者发生）为低镁血症[7例（23.3%）]和皮疹[2例（6.7%）]。未发生治疗相关死亡。
SCT200单药作为晚期ESCC的二线或后续治疗显示出良好疗效，安全性可接受。TP53突变丰度可能是一种潜在的预测生物标志物。
