Efficacy and safety of dual blockade of HER2 and PD-1 in patients with HER2-positive gastric cancer: a retrospective, multicentre study

• Published in: Scientific reports 2024-10, Vol.14 (1), p.25030-11, Article 25030
• Main Authors: Cen, Shuyi, Yuan, Meiqin, Sun, Qunan, Hou, Guilan, Ying, Jieer, Xu, Qi, Zheng, Yu, Dong, Ying, Pan, Hongming, Han, Weidong
• Format: Article
• Language: English
• Subjects: 692/4028/67/1059/2325; 692/4028/67/1504/1829; Adult; Aged; Aged, 80 and over; Anti-PD-1; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Cancer therapies; Chemotherapy; Combination therapy; ErbB-2 protein; Female; Gastric cancer; HER2; Humanities and Social Sciences; Humans; Immune checkpoint inhibitors; Immune Checkpoint Inhibitors - adverse effects; Immune Checkpoint Inhibitors - therapeutic use; Immunotherapy; Male; Middle Aged; multidisciplinary; Patients; PD-1 protein; Programmed Cell Death 1 Receptor - antagonists & inhibitors; Programmed Cell Death 1 Receptor - metabolism; Receptor, ErbB-2 - antagonists & inhibitors; Receptor, ErbB-2 - metabolism; Response rates; Retrospective Studies; Science; Science (multidisciplinary); Side effects; Solid tumors; Stomach Neoplasms - drug therapy; Stomach Neoplasms - metabolism; Stomach Neoplasms - mortality; Stomach Neoplasms - pathology; Survival; Targeted therapy; Trastuzumab; Trastuzumab - therapeutic use; Treatment Outcome
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-024-76296-y

Human epidermal growth factor receptor 2 (HER2) expression is one of the most important pathological characteristics of gastric cancer. The positive rate of HER2 expression in patients with gastric cancer is approximately 20%. The phase III Keynote-811 study revealed that anti-HER2 and anti-PD-1 therapy combined with chemotherapy could significantly improve the objective response rate as first-line treatment in patients with HER2-positive advanced gastric cancer. In the present study, we aimed to evaluate the efficacy of combination therapy with trastuzumab and PD-1 inhibitors in patients with advanced HER2-positive gastric cancer in a real-world setting. Seventy-two HER2-positive gastric cancer patients from three hospitals in China were retrospectively reviewed. These patients were treated with trastuzumab plus one anti-PD-1 agent with or without chemotherapy. The overall response rate, progression-free survival and overall survival were assessed according to the Response Evaluation Criteria in Solid Tumours (RECIST 1.1). From January 2018 to October 2021, 72 patients with HER2-positive gastric cancer received trastuzumab and a PD-1 inhibitor with or without chemotherapy as neoadjuvant chemotherapy, first-line therapy, second-line therapy or salvage therapy. The ORR was 54.2% for all patients and 79.4% for previously untreated patients. The median PFS and median OS were 10 months (95% CI: 8–13 months) and 26.1 months (95% CI: 18.5-NA months), respectively, for all patients. Grade 3 adverse effects occurred in approximately 25% of patients. Immune-related adverse effects occurred in approximately 12.5% of patients. Trastuzumab and PD-1 inhibitor combination therapy with or without chemotherapy achieved satisfactory survival outcomes in patients with HER2-positive gastric cancer with acceptable safety.