Zhongkuo Zhao, Shuai Wang, Rui Dong, Xiaohui Yang, Fei Lu
Our report indicates that although HER2 positivity is rare, occurring in approximately 4% of SMARCA4-mutated gastric cancers, the combination of disitamab vedotin and PD-1 inhibition may still provide meaningful therapeutic benefit, as demonstrated by the effective control of liver metastasis in our case. However, because SMARCA4-mutated gastric cancer is extremely uncommon, further clinical evidence based on larger patient cohorts is needed to confirm the reliability of this therapeutic strategy and to determine its impact on long-term survival outcomes.
BACKGROUND: SMARCA4-mutated gastric cancer is an extremely rare upper gastrointestinal malignancy characterized by high aggressiveness, early metastatic spread, poor response to chemo-radiotherapy, and dismal prognosis.
CASE PRESENTATION: Here, we report a case of SMARCA4-mutated undifferentiated gastric carcinoma. The patient was initially diagnosed by gastroscopy and pathological examination, followed by radical gastrectomy. Postoperatively, programmed cell death protein 1 (PD-1) blockade with tislelizumab was administered. However, disease progression occurred, and liver metastasis was identified on CT three months after surgery. The patient subsequently received tislelizumab in combination with the HER2-targeted antibody-drug conjugate (ADC) disitamab vedotin. Under this combination regimen, the liver metastatic lesions progressively regressed and completely disappeared after six months of treatment. To date, the patient remains in good clinical condition with a progression-free survival (PFS) of 26 months.
CONCLUSION: Our report indicates that although HER2 positivity is rare, occurring in approximately 4% of SMARCA4-mutated gastric cancers, the combination of disitamab vedotin and PD-1 inhibition may still provide meaningful therapeutic benefit, as demonstrated by the effective control of liver metastasis in our case. However, because SMARCA4-mutated gastric cancer is extremely uncommon, further clinical evidence based on larger patient cohorts is needed to confirm the reliability of this therapeutic strategy and to determine its impact on long-term survival outcomes.