Weill Cornell Medical College, New York City, NY, USA.
Department of Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa City, Japan.
Nat Med. 2023 Aug;29(8):2133-2141. doi: 10.1038/s41591-023-02465-7. Epub 2023 Jul 31.
There is an urgent need for first-line treatment options for patients with human epidermal growth factor receptor 2 (HER2)-negative, locally advanced unresectable or metastatic gastric or gastroesophageal junction (mG/GEJ) adenocarcinoma. Claudin-18 isoform 2 (CLDN18.2) is expressed in normal gastric cells and maintained in malignant G/GEJ adenocarcinoma cells. GLOW (closed enrollment), a global, double-blind, phase 3 study, examined zolbetuximab, a monoclonal antibody that targets CLDN18.2, plus capecitabine and oxaliplatin (CAPOX) as first-line treatment for CLDN18.2-positive, HER2-negative, locally advanced unresectable or mG/GEJ adenocarcinoma. Patients (n = 507) were randomized 1:1 (block sizes of two) to zolbetuximab plus CAPOX or placebo plus CAPOX. GLOW met the primary endpoint of progression-free survival (median, 8.21 months versus 6.80 months with zolbetuximab versus placebo; hazard ratio (HR) = 0.687; 95% confidence interval (CI), 0.544-0.866; P = 0.0007) and key secondary endpoint of overall survival (median, 14.39 months versus 12.16 months; HR = 0.771; 95% CI, 0.615-0.965; P = 0.0118). Grade ≥3 treatment-emergent adverse events were similar with zolbetuximab (72.8%) and placebo (69.9%). Zolbetuximab plus CAPOX represents a potential new first-line therapy for patients with CLDN18.2-positive, HER2-negative, locally advanced unresectable or mG/GEJ adenocarcinoma. ClinicalTrials.gov identifier: NCT03653507 .
对于人表皮生长因子受体 2（HER2）阴性、局部晚期不可切除或转移性胃或胃食管交界处（mG/GEJ）腺癌患者，迫切需要一线治疗选择。Claudin-18 同种型 2（CLDN18.2）在正常胃细胞中表达，并在恶性 G/GEJ 腺癌细胞中保持。GLOE（封闭入组）是一项全球性、双盲、3 期研究，评估了靶向 CLDN18.2 的单克隆抗体 zolbetuximab 联合卡培他滨和奥沙利铂（CAPOX）作为 CLDN18.2 阳性、HER2 阴性、局部晚期不可切除或 mG/GEJ 腺癌的一线治疗。患者（n=507）按 1:1（分组大小为 2）随机分配至 zolbetuximab 加 CAPOX 或安慰剂加 CAPOX。GLOE 达到了无进展生存期（中位，8.21 个月与 zolbetuximab 组的 6.80 个月与安慰剂组；风险比（HR）=0.687；95%置信区间（CI），0.544-0.866；P=0.0007）和总生存期的关键次要终点（中位，14.39 个月与 12.16 个月；HR=0.771；95%CI，0.615-0.965；P=0.0118）。zolbetuximab（72.8%）和安慰剂（69.9%）的 3 级及以上治疗后出现的不良事件相似。zolbetuximab 加 CAPOX 代表了 CLDN18.2 阳性、HER2 阴性、局部晚期不可切除或 mG/GEJ 腺癌患者新的一线治疗选择。临床试验编号：NCT03653507。
