关于局部晚期 (LA) 不可切除或转移性胃或胃食管交界处 (mG/GEJ) 腺癌患者中密蛋白 18 异构体 2 (CLDN18.2) 阳性的全球患病率以及 CLDN18.2 状态与临床和肿瘤特征之间的关联，数据有限。我们报告了 CLDN18.2 阳性率（第 3 期；SPOTLIGHT，NCT03504397；GLOW，NCT03653507）以及配对肿瘤样本子集（第 2 期，ILUSTRO，NCT03505320；第 1 期，NCT03528629）之间 CLDN18.2 状态的一致性。 zolbetuximab 的临床研究。通过免疫组织化学检测来自 LA 不可切除或 mG/GEJ 腺癌患者的肿瘤样本的 CLDN18.2 状态。根据中央或局部评估测试人表皮生长因子受体 2 (HER2) 表达。在 SPOTLIGHT 和 GLOW 中，CLDN18.2 阳性的患病率（≥75% 的肿瘤细胞表现出中度至强膜 CLDN18 染色）为 38.4% 。无论采集方法（活检与切除）或采集部位（原发性与转移性）如何，胃腺癌样本与 GEJ 腺癌样本的患病率相似。 CLDN18.2 阳性在弥漫型肿瘤患者中最为普遍。在 ILUSTRO 和 1 期研究中，存档（即治疗前的任何时间）和基线（即首次治疗前 ≤ 3 个月）样本之间 CLDN18.2 阳性的一致性为 61.1%，并且任何 CLDN18 染色的一致性（≥ 1）表现出中度至强膜 CLDN18 染色的肿瘤细胞百分比为 88.9%。CLDN18.2 是 HER2 阴性、LA 不可切除或 mG/GEJ 腺癌患者中高度普遍的生物标志物。许多患者的 CLDN18.2 阳性随着时间的推移保持相对稳定。应在这些患者的标准临床实践中考虑对 CLDN18.2 进行生物标志物检测。© 2024。作者。

Limited data exist for global prevalence of claudin 18 isoform 2 (CLDN18.2) positivity and association of CLDN18.2 status with clinical and tumor characteristics in patients with locally advanced (LA) unresectable or metastatic gastric or gastroesophageal junction (mG/GEJ) adenocarcinoma. We report prevalence of CLDN18.2 positivity (phase 3; SPOTLIGHT, NCT03504397; GLOW, NCT03653507) and concordance of CLDN18.2 status between a subset of pair-matched tumor samples (phase 2, ILUSTRO, NCT03505320; phase 1, NCT03528629) from clinical studies of zolbetuximab.Tumor samples from patients with LA unresectable or mG/GEJ adenocarcinoma were tested for CLDN18.2 status by immunohistochemistry. Human epidermal growth factor receptor 2 (HER2) expression was tested per central or local assessment.Across SPOTLIGHT and GLOW, the prevalence of CLDN18.2 positivity (≥ 75% of tumor cells demonstrating moderate-to-strong membranous CLDN18 staining) was 38.4%. Prevalence was similar in gastric versus GEJ adenocarcinoma samples and regardless of collection method (biopsy versus resection) or collection site (primary versus metastatic). CLDN18.2 positivity was most prevalent in patients with diffuse-type tumors. In ILUSTRO and the phase 1 study, concordance of CLDN18.2 positivity was 61.1% between archival (i.e., any time before treatment) and baseline (i.e., ≤ 3 months before first treatment) samples, and concordance of any CLDN18 staining (≥ 1% of tumor cells demonstrating moderate-to-strong membranous CLDN18 staining) was 88.9%.CLDN18.2 was a highly prevalent biomarker in patients with HER2-negative, LA unresectable or mG/GEJ adenocarcinoma. CLDN18.2 positivity remained relatively stable over time in many patients. Biomarker testing for CLDN18.2 should be considered in standard clinical practice in these patients.© 2024. The Author(s).