Human epidermal growth factor receptor 2 (HER2)-positive gastric cancer is a subtype for which new drugs and specific treatment strategies should be developed. Trastuzumab deruxtecan (T-DXd) is a novel HER2-targeted antibody–drug conjugate containing topoisomerase I inhibitor as a payload. In the randomized phase 2 study (DESTINY-Gastric01) for HER2-positive advanced gastric or gastroesophageal junction cancer (AGC), patients treated with T-DXd showed a significantly higher response rate compared with the chemotherapy of physician’s choice, associated with remarkably prolonged progression-free and overall survival. T-DXd also exhibits anti-tumor activity to HER2-negative tumor cells close to HER2-positive cells (so-called bystander killing effect). T-DXd was effective even for HER2-low expressing breast and gastric cancer in several clinical studies. Taking advantage of these strong points and synergism with other cytotoxic, molecular-targeted and immunological agents, it is expected that T-DXd will bring further progression in treatment both for strongly and weakly HER2 positive AGC in various treatment settings including perioperative chemotherapy.

人表皮生长因子受体 2 (HER2) 阳性胃癌是一种亚型，应针对该亚型开发新的药物和特定的治疗策略。Trastuzumab deruxtecan (T-DXd) 是一种新型 HER2 靶向抗体-药物偶联物，含有拓扑异构酶 I 抑制剂作为有效载荷。在 HER2 阳性晚期胃癌或胃食管交界处癌 (AGC) 的随机 2 期研究 (DESTINY-Gastric01) 中，与医生选择的化疗相比，接受 T-DXd 治疗的患者显示出显着更高的缓解率，并与显着延长的进展相关-免费和总生存。T-DXd 还对 HER2 阳性细胞附近的 HER2 阴性肿瘤细胞表现出抗肿瘤活性（所谓的旁观者杀伤效应）。在多项临床研究中，T-DXd 甚至对 HER2 低表达的乳腺癌和胃癌也有效。利用这些优势以及与其他细胞毒性、分子靶向和免疫学药物的协同作用，预计 T-DXd 将在包括围手术期化疗在内的各种治疗环境中为强和弱 HER2 阳性 AGC 的治疗带来进一步的进展。