Ishii Takahiro, Shitara Kohei
Department of Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, Japan.
Department of Experimental Therapeutics, National Cancer Center Hospital East, Kashiwa, Japan.
Expert Rev Anticancer Ther. 2021 Nov;21(11):1193-1201. doi: 10.1080/14737140.2021.1982698. Epub 2021 Sep 29.
Although various new drugs have been developed, the prognosis of therapeutic advances for metastatic gastric cancer is insufficient. Trastuzumab deruxtecan (T-DXd), a new human epidermal growth factor receptor 2 (HER2)-targeting antibody-drug conjugate (ADC), has demonstrated promising results in clinical trials.
In this article, we review the history of anti-HER2 ADCs and focus on the efficacy and safety of T-DXd and describe the development of new anti-HER2 drugs.
So far, no other anti-HER2 ADCs have demonstrated efficacy in patients with HER2-positive advanced gastric cancer with two or more previous lines of chemotherapy, including trastuzumab. However, a new drug, T-DXd, has shown a significantly higher objective response rate and a longer overall survival and, thus, was approved in Japan. In the future, new anti-HER2 drugs and/or treatment strategies including T-DXd along with cytotoxic chemotherapy or immune checkpoint inhibitors will be developed.
尽管已研发出多种新药，但转移性胃癌治疗进展的预后仍不尽人意。曲妥珠单抗德瓦鲁单抗（T-DXd）是一种新型的靶向人表皮生长因子受体2（HER2）的抗体药物偶联物（ADC），在临床试验中已显示出有前景的结果。
在本文中，我们回顾了抗HER2 ADC的历史，并重点关注T-DXd的疗效和安全性，并描述新型抗HER2药物的研发情况。
到目前为止，包括曲妥珠单抗在内，尚无其他抗HER2 ADC在接受过两线或更多线化疗的HER2阳性晚期胃癌患者中显示出疗效。然而，一种新药T-DXd已显示出显著更高的客观缓解率和更长的总生存期，因此在日本获得批准。未来，将研发包括T-DXd在内的新型抗HER2药物和/或治疗策略，联合细胞毒性化疗或免疫检查点抑制剂。
