AUTHOR=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 TITLE=Case report: Long response to PD-1 blockade after failure of trastuzumab plus chemotherapy in advanced Epstein-Barr virus-associated gastric cancer JOURNAL=Frontiers in Immunology VOLUME=13 YEAR=2022 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.1003859 DOI=10.3389/fimmu.2022.1003859 ISSN=1664-3224 ABSTRACT=Background

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.

Case Presentation

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 in situ 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.

Summary

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.