ReviewHopes and failures in front-line advanced HER2-positive gastric cancer therapyKong, Fanminga,,b,,*; Yao, Yanga,,b,,*; Deng, Renfena,,b; Li, Xiaojianga,,b; Jia, Yingjiea,,b Author Information aDepartment of Oncology, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine bNational Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, Tianjin, People’s Republic of China *Fanming Kong and Yang Yao contributed equally to the writing of this article. Received 8 September 2020 Revised form accepted 20 March 2021 Correspondence to Yingjie Jia, PhD, Department of Oncology, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Anshanxi Road, Nankai District, 300193 Tianjin, People’s Republic of China, Tel: + 86 22 27986556; e-mail: [email protected] Anti-Cancer Drugs 32(7):p 675-680, August 2021. | DOI: 10.1097/CAD.0000000000001081 Buy Metrics Abstract Human epidermal growth-factor receptor 2 (HER2) was an important therapeutic target in gastric cancer. Through the last decade, strategy with trastuzumab-based chemotherapy remains the first-line standard of treatment in advanced HER2-positive gastric cancer. Based on the Trastuzumab for Gastric Cancer trial, trastuzumab plus systemic chemotherapy of cisplatin and fluoropyrimidine as the backbone was established as the first-line therapy in advanced HER2-positive gastric cancer. Since then, studies have explored the optimization of the front-line strategy, including the dose of trastuzumab, chemotherapy regimen and maintenance therapy. A large number of clinical trials were conducted to explore the optimal front-line therapy regimens, such as lapatinib and pertuzumab. Safe and effective first-line regimens are still lacking. Recently, two phase II studies of combining immune checkpoint inhibitor in first-line treatment of advanced HER2-positive gastric cancer showed promising results. The progress of immunotherapy has gradually promoted the development of front-line treatment of advanced HER2-positive gastric cancer to potential chemotherapy-free strategies. Therefore, this article reviewed these significant clinical trials and focus on the front-line treatment strategies for HER2-positive gastric cancer. Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.