Case report: Long response to PD-1 blockade after failure of trastuzumab plus chemotherapy in advanced Epstein-Barr virus-associated gastric cancer

• Published in: Frontiers in immunology 2022-10, Vol.13, p.1003859
• Main Authors: Pan, Yan, Lu, Linbin, Liu, Huan, Chen, Di, Han, Ning, Yao, Ruirong, Wang, Xinlin, Gao, Xianchun, Yu, Jun, Chen, Ling, Zhou, Fenli, Hao, Guangjun, Lu, Yuanyuan, Li, Mengbin, He, Guangbin, Kang, Fei, Li, Zengshan, Tang, Yongqiang, Zhang, Jinsong, Wei, Lichun, Nie, Yongzhan
• Format: Article
• Language: English
• Subjects: B7-H1 Antigen - genetics; Epstein-Barr virus; Epstein-Barr Virus Infections - complications; gastric cancer; HER2; Herpesvirus 4, Human; Humans; Immunology; immunotherapy; Male; Middle Aged; PD-1; Positron Emission Tomography Computed Tomography; Stomach Neoplasms - pathology; Trastuzumab - therapeutic use
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2022.1003859

Trastuzumab-containing chemotherapy is the first-line treatment for advanced gastric cancer (GC) with HER2 positive. Although PD-1 inhibitors significantly improved the outcome of GC patient's refractory to previous chemotherapy regimens, few studies explore the role of anti-PD-1 therapy overcomes resistance to trastuzumab plus chemotherapy in advanced Epstein-Barr Virus-associated gastric cancer (EBVaGC) with PD-L1 and HER2 positive. We report a case of advanced EBVaGC in a 45-year-old man presenting with fatigue, dysphagia, and weight loss for several months. Initial endoscopy revealed a large tumor at the gastroesophageal junction. Computed tomography revealed GC accompanied by multiple lymph nodes and hepatic and pulmonary metastases. The immunohistochemistry indicated that HER-2 and PD-L1 were overexpressed, and tumor cells were positive for EBV-encoded small RNA (EBER) by hybridization. Trastuzumab plus DCS was started as first-line chemotherapy with a PFS of 4 months and shifted to trastuzumab plus FOLFIRI or gemcitabine as second-/third-line therapy. After five-cycle nivolumab monotherapy, the patient received partial response and was treated with total radical gastrectomy plus sequential radiotherapy. He continued the postoperative immunotherapy over 30 cycles with a PFS of 28 months. Due to a new abdominal lymph node metastasis confirmed by PET-CT, he received toripalimab as the next-line treatment and achieved complete remission as the best objective response. We presented an advanced HER2-positive EBVaGC patient with PD-L1 high expression, refractory to trastuzumab plus chemotherapy, and had a durable clinical benefit sequence with a single dose of the PD-1 inhibitor.