Published online Mar 16, 2022. doi: 10.12998/wjcc.v10.i8.2497
Peer-review started: July 26, 2021
First decision: October 22, 2021
Revised: October 25, 2021
Accepted: January 29, 2022
Article in press: January 29, 2022
Published online: March 16, 2022
Processing time: 227 Days and 17.2 Hours
Immune checkpoint inhibitors (ICIs) targeting the programmed death (PD)-1 pathway have substantially changed the clinical management of metastatic urothelial carcinoma (mUC); 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.
We present a 59-year-old man with mUC 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.
ERBB2/3 mutations may represent a predictive biomarker for selecting a subgroup of mUC patients who will benefit from ICIs.
Core tip: Immune checkpoint inhibitors (ICIs) have substantially changed the clinical management of metastatic urothelial carcinoma (mUC); however, the response rate to monotherapy remains low. Previous studies have suggested that ERBB2/3 mutations are associated with the efficacy of ICIs in gallbladder carcinoma. The present case of mUC harboring ERBB2/3 mutations, negative programmed death (PD)-ligand 1 expression, and low tumor mutation burden showed durable response to anti-PD-1 antibodies combined with paclitaxel as second-line treatment. Further studies are required to investigate this finding.