Division of Gastrointestinal Medical Oncology, National Cancer Center Hospital, 5-1-1, Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan.
Gastric Cancer. 2021 May;24(3):567-576. doi: 10.1007/s10120-021-01164-x. Epub 2021 Mar 1.
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）阳性胃癌是一种需要开发新药和特定治疗策略的亚型。曲妥珠单抗-美坦新偶联物（T-DXd）是一种新型的 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。在针对 HER2 阳性晚期胃癌或胃食管结合部癌（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 治疗的患者显示出更高的缓解率，与显著延长的无进展生存期和总生存期相关。T-DXd 还对接近 HER2 阳性细胞的 HER2 阴性肿瘤细胞具有抗肿瘤活性（所谓旁观者杀伤效应）。在几项临床研究中，T-DXd 对 HER2 低表达的乳腺癌和胃癌也显示出疗效。利用这些优势以及与其他细胞毒性、分子靶向和免疫治疗药物的协同作用，T-DXd 有望在包括围手术期化疗在内的各种治疗环境中，为强阳性和弱阳性 HER2 阳性 AGC 的治疗带来进一步的进展。
