%A Xu,Zhenying %A Ma,Jiaman %A Chen,Ting %A Yang,Yu %D 2022 %J Frontiers in Immunology %C %F %G English %K Urothelial carcinoma (UC),Human Epidermal Growth Factor Receptor 2 (HER2),Trastuzumab (Herceptin),Pembrolizumab,Antibody-drug conjugates (ADC),RC48-ADC %Q %R 10.3389/fimmu.2022.978266 %W %L %M %P %7 %8 2022-November-15 %9 Case Report %+ Yu Yang,Department of Abdominal Oncology, West China Hospital, Sichuan University,China,yangyu@wchscu.cn %# %! Pembrolizumab combined RC48 in mUC %* %< %T Case report: The remarkable response of pembrolizumab combined with RC48 in the third-line treatment of metastatic urothelial carcinoma %U https://www.frontiersin.org/articles/10.3389/fimmu.2022.978266 %V 13 %0 JOURNAL ARTICLE %@ 1664-3224 %X BackgroundSystemic 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 presentationHere, 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 had 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 a 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 25 August 2022. There are no grade 3 or 4 adverse events or aggravations of renal insufficiency during the third-line therapy.DiscussionRC48 combined with pembrolizumab demonstrated outstanding efficacy and safety in this HER2-positive metastatic UC patient. ADC combined with ICI is a promising anti-tumor strategy that deserves further exploration in advanced UC.