Abstract
BACKGROUND: Although targeted therapy provides survival benefits for patients with metastatic colorectal cancer, some patients develop resistance to these treatments. Human epidermal growth factor receptor 2 (HER2) is overexpressed in a subset of patients with colorectal cancer and has been established as a therapeutic target. CASE SUMMARY: This case report describes a Chinese patient with HER2-amplified advanced rectal cancer who showed no response to chemotherapy and targeted therapies against epidermal growth factor receptor and vascular endothelial growth factor but achieved a remarkable response following treatment with immune checkpoint inhibitors (ICIs) in combination with pyrotinib. The combination of oxaliplatin and ICIs with pyrotinib demonstrates synergistic effects after late-stage disease progression. CONCLUSION: ICIs and pyrotinib may be effective in treating HER2-amplified advanced rectal cancer. Chemotherapy following disease progression could enhance efficacy synergistically.