AUTHOR=Xu Zhenying , Ma Jiaman , Chen Ting , Yang Yu 

TITLE=Case report: The remarkable response of pembrolizumab combined with RC48 in the third-line treatment of metastatic urothelial carcinoma

JOURNAL=Frontiers in Immunology

VOLUME=Volume 13 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.978266

DOI=10.3389/fimmu.2022.978266

ISSN=1664-3224

ABSTRACT=Background Systemic chemotherapy has been the mainstay treatment for locally advanced or metastatic urothelial carcinoma (UC). In the past few years, novel immune checkpoint inhibitors (ICIs) and antibody-drug conjugates (ADCs) have improved the treatment of advanced UC. Case presentation Here, we report systemic therapy of a 68-year-old male diagnosed with HER2 positive (immunohistochemistry 3+), programmed cell death ligand 1(PD-L1) negative metastatic UC and renal insufficiency. He has encountered numerous metastases and failed first-line platinum-based chemotherapy and second-line treatment with pembrolizumab and trastuzumab. During third-line treatment with RC48 (a HER2 targeting ADC) combined with pembrolizumab, he achieved rapid partial response (PR) in the first evaluation and subsequent complete response (CR) on PET/CT and long-term progression-free survival (> 12 months) at the last follow-up on Aug 25, 2022. Grade 3 or 4 adverse events or aggravation of renal insufficiency do not occur during the third-line therapy. Discussion RC48 combined with pembrolizumab demonstrated outstanding efficacy and safety in this HER2-positive metastatic UC patient. ADC combined with ICIs is a promising anti-tumor strategy that deserves further exploration in advanced UC.