Metastatic urothelial carcinoma harboring ERBB2/3 mutations dramatically respond to chemotherapy plus anti-PD-1 antibody:A case report

BACKGROUND Immune checkpoint inhibitors(ICIs)targeting the programmed death(PD)-1 pathway have substantially changed the clinical management of metastatic urothelial carcinoma(m UC);however,the response rate remains low.There are ongoing efforts to identify robust biomarkers that can effectively predict the treatment response to ICIs.Previous studies have suggested that ERBB2/3 mutations are associated with the efficacy of ICIs in gallbladder carcinoma.CASE SUMMARY We present a 59-year-old man with m UC harboring ERBB2/3 mutations(in-frame insertion of ERBB2 and ERBB3 amplification),negative PD-ligand 1 expression,and low tumor mutation burden.He received anti-PD-1 antibodies and paclitaxel as second-line treatment.After two cycles of treatment,the lung metastases had significantly shrunk,achieving good partial remission.After six cycles of combination therapy,the patient received sindilimab 200 mg once every 3 wk as maintenance monotherapy.At the last follow-up,the patient continued to exhibit a partial response and progression-free survival for as long as 19 mo.CONCLUSION ERBB2/3 mutations may represent a predictive biomarker for selecting a subgroup of m UC patients who will benefit from ICIs.