Globally, the fifth most common cancer and the fourth leading cause of cancer-related mortality is gastric cancer (GC). Recent clinical trials on solid tumors enrolled patients who possess druggable genetic alterations, protein expression, and immune characteristics. In gastric or gastroesophageal junction (GEJ) cancers, trastuzumab combined with first-line chemotherapy in human epidermal growth factor receptor 2 (HER2)-positive patients and ramucirumab combined with second-line paclitaxel remarkably prolonged overall survival (OS) compared with chemotherapy alone, according to phase 3 trial results. Recently, immune checkpoint inhibitor (ICI) monotherapy was approved as third- or later-line treatment. Chemotherapy plus ICIs as first-line treatment exhibited improved survival compared with chemotherapy alone in HER2-negative patients according to Checkmate 649 trial results. Conversely, systemic chemotherapy prognosis remains poor. although some patients may achieve durable response to treatment and prolonged survival in advanced GC. Recently, a first-in-class, chimeric immunoglobulin G1 monoclonal antibody (zolbetuximab) that targets and binds to claudin 18 isoform 2 (CLDN18.2) has emerged as a new target therapy in GC treatment. Global phase Ⅲ trials revealed that the addition of zolbetuximab to first-line chemotherapy prolonged OS in CLDN18.2-positive and HER2-negative GC patients. This review summarizes recent clinical trials of CLDN18.2-targeted therapy.
在全球范围内，胃癌是第五大常见癌症，也是癌症相关死亡的第四大主要原因。近期针对实体瘤的临床试验纳入了具有可靶向基因改变、蛋白表达及免疫特征的患者。根据三期临床试验结果，在胃或胃食管结合部癌中，人表皮生长因子受体2阳性患者接受曲妥珠单抗联合一线化疗，以及雷莫西尤单抗联合二线紫杉醇治疗，与单纯化疗相比显著延长了总生存期。最近，免疫检查点抑制剂单药疗法已被批准作为三线或后线治疗。根据Checkmate 649试验结果，在人表皮生长因子受体2阴性患者中，化疗联合免疫检查点抑制剂作为一线治疗相比单纯化疗显示出生存获益。然而，尽管部分晚期胃癌患者可能获得持久治疗反应并延长生存期，全身化疗的预后仍然较差。近期，一种首创的靶向并结合紧密连接蛋白18亚型2的嵌合免疫球蛋白G1单克隆抗体（zolbetuximab）已成为胃癌治疗的新靶向疗法。全球三期临床试验表明，在紧密连接蛋白18亚型2阳性且人表皮生长因子受体2阴性的胃癌患者中，一线化疗联合zolbetuximab可延长总生存期。本综述总结了近期针对紧密连接蛋白18亚型2靶向治疗的临床试验进展。
肿瘤(癌症)患者之家