Case Report
Copyright ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Cases. Mar 16, 2022; 10(8): 2497-2503
Published online Mar 16, 2022. doi: 10.12998/wjcc.v10.i8.2497
Metastatic urothelial carcinoma harboring ERBB2/3 mutations dramatically respond to chemotherapy plus anti-PD-1 antibody: A case report
Fei-Fei Yan, Qi Jiang, Bin Ru, Xiao-Jie Fei, Jian Ruan, Xiao-Chen Zhang
Fei-Fei Yan, Qi Jiang, Xiao-Chen Zhang, Department of Medical Oncology, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310000, Zhejiang Province, China
Bin Ru, Department of Pain Medicine, Zhejiang Provincial People’s Hospital, Hangzhou 310000, Zhejiang Province, China
Xiao-Jie Fei, Department of Surgical Oncology, the First Affiliated Hospital, Zhejiang University School of Medicine Hangzhou 313000, Zhejiang Province, China
Jian Ruan, Department of Medical Oncology, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang Province, China
Author contributions: Yan FF, Jiang Q, and Zhang XC were the patient’s oncologists, reviewed the literature, and contributed to manuscript drafting; Ru B and Fei XJ analyzed and interpreted the imaging findings; Ruan J and Zhang XC reviewed and edited the manuscript; Yan FF and Jiang Q contributed equally to this work; all authors read and approved the final manuscript.
Supported by the Zhejiang Medical Association, No. 2018ZYC-A18.
Informed consent statement: Informed written consent was obtained from the patient for publication of this report and any accompanying images.
Conflict-of-interest statement: The authors declare that they have no conflict of interest.
CARE Checklist (2016) statement: The authors have read the CARE Checklist (2016), and the manuscript was prepared and revised according to the CARE Checklist (2016).
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Xiao-Chen Zhang, Doctor, MD, Associate Chief Physician, Chief Physician, Doctor, Department of Medical Oncology, The First Affiliated Hospital, College of Medicine, Zhejiang University, No. 79 Qingchun Road, Hangzhou 310000, Zhejiang Province, China. zhangxiaochen@zju.edu.cn
Received: July 26, 2021
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
Abstract
BACKGROUND

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.

CASE SUMMARY

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.

CONCLUSION

ERBB2/3 mutations may represent a predictive biomarker for selecting a subgroup of mUC patients who will benefit from ICIs.

Keywords: Urothelial carcinoma, Bladder cancer, ERBB, Programmed death, Sindilimab, Case report

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.