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

Abstract

BackgroundTrastuzumab-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 PresentationWe 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.SummaryWe 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.

Immune checkpoint inhibitors are effective in the treatment of Epstein-Barr virus-associated gastric cancer: A case report

“…Lv et al [ 19 ] reported a patient with EBVaGC (PD-L1 +) who achieved therapeutic effect and a manageable safety profile (PFS was at least 12 months) after treatment with camrelizumab combined with SOX. Pan et al [ 20 ] also reported a patient with advanced EBVaGC (high expression of PD-L1 and HER-2) who experienced tumor regression and 28 months of PFS with nivolumab treatment, after not responding to trastuzumab combined with chemotherapy. At present, there are few clinical studies of ICIs for the treatment of EBVaGC, but the existing studies suggest that immunotherapy shows better efficacy and manageable adverse effects in EBVaGC.…”

Effect of anlotinib combined with camrelizumab on clinical efficacy and short-term prognosis in male patients with advanced gastric cancer

“…By inhibiting PD-1, T cell activity can be improved, bolstering their ability to combat tumors. This principle underpins the effectiveness of PD-1 inhibitors in treating advanced solid malignancies [15][16][17].…”