Antibody-drug conjugates induced a durable response in trastuzumab-resistant HER2-positive gastric cancer: A case report and review of literature

BACKGROUND Gastric cancer (GC) is the fourth leading cause of cancer-related mortality worldwide.First-line treatment for human epidermal growth factor receptor 2 (HER2)-positive advanced GC is primarily based on chemotherapy combined with trastuzumab.However, the median overall survival of advanced GC is only about 12 months.No standard consensus second-line treatment has been established for patients with HER2-positive advanced GC following progression on trastuzumabbased therapy.CASE SUMMARY A 72-year-old man with remnant GC underwent curative surgery followed by adjuvant chemotherapy combined with trastuzumab.One year later, follow-up computed tomography revealed newly developed liver and bone metastases.Liver biopsy confirmed metastatic gastric adenocarcinoma, and immunohistochemistry demonstrated HER2 overexpression (3+) and programmed death ligand 1 (combined positive score: 5).The patient subsequently received disitamab vedotin in combination with sintilimab for 1 year.Owing to grade 3 peripheral neuropathy, disitamab vedotin was discontinued, while sintilimab monotherapy was continued for an additional year.The patient ultimately achieved sustained disease control and complete remission of the liver metastasis, with an overall survival exceeding 48 months to date.CONCLUSION This case highlights the potential of sequential HER2-targeted antibody-drug conjugate therapy combined with immunotherapy to achieve long-term survival in trastuzumab-resistant metastatic GC.