Journal of the National Cancer Center (Jun 2023)
Assessment of the expression pattern of HER2 and its correlation with HER2-targeting antibody-drug conjugate therapy in urothelial cancer
- Huizi Lei,
- Yun Ling,
- Pei Yuan,
- Xieqiao Yan,
- Lin Wang,
- Yanxia Shi,
- Xin Yao,
- Hong Luo,
- Benkang Shi,
- Jiyan Liu,
- Zhisong He,
- Guohua Yu,
- Weiqing Han,
- Changlu Hu,
- Zhihong Chi,
- Chuanliang Cui,
- Lu Si,
- Jianmin Fang,
- Jun Guo,
- Xinan Sheng,
- Aiping Zhou,
- Jianming Ying
Affiliations
- Huizi Lei
- Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- Yun Ling
- Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- Pei Yuan
- Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- Xieqiao Yan
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Renal Cancer and Melanoma, Peking University Cancer Hospital & Institute, Beijing, China
- Lin Wang
- Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- Yanxia Shi
- Department of Medical Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China
- Xin Yao
- Department of Genitourinary Oncology, National Clinical Research Center for Cancer, Tianjin Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China
- Hong Luo
- Department of Genitourinary Oncology, Chongqing University Cancer Hospital and Chongqing Cancer Institute and Chongqing Cancer Hospital, Chongqing, China
- Benkang Shi
- Department of Urology, Qilu Hospital of Shandong University, Jinan, China
- Jiyan Liu
- Department of Biotherapy, Cancer Center, National Clinical Research Center for Geriatrics, West China Hospital of Sichuan University, Chengdu, China
- Zhisong He
- Department of Urology, Peking University First Hospital, Institute of Urology, National Urological Cancer Center of China, Peking University, Beijing, China
- Guohua Yu
- Department of Medical Oncology, Weifang People's Hospital, Weifang, China
- Weiqing Han
- Department of Urology, Hunan Cancer Hospital/The Affiliated Cancer Hospital of Xiangya School of Medicine of Central South University, Changsha, China
- Changlu Hu
- Department of Medical Oncology, Anhui Provincial Cancer Hospital, Hefei, China
- Zhihong Chi
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Renal Cancer and Melanoma, Peking University Cancer Hospital & Institute, Beijing, China
- Chuanliang Cui
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Renal Cancer and Melanoma, Peking University Cancer Hospital & Institute, Beijing, China
- Lu Si
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Renal Cancer and Melanoma, Peking University Cancer Hospital & Institute, Beijing, China
- Jianmin Fang
- RemeGen Co., Ltd., Yantai, Shandong, China; School of Life Science and Technology, Tongji University, Shanghai, China
- Jun Guo
- Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China; Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Renal Cancer and Melanoma, Peking University Cancer Hospital & Institute, Beijing, China; Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China; Department of Medical Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China; Department of Genitourinary Oncology, National Clinical Research Center for Cancer, Tianjin Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China; Department of Genitourinary Oncology, Chongqing University Cancer Hospital and Chongqing Cancer Institute and Chongqing Cancer Hospital, Chongqing, China; Department of Urology, Qilu Hospital of Shandong University, Jinan, China; Department of Biotherapy, Cancer Center, National Clinical Research Center for Geriatrics, West China Hospital of Sichuan University, Chengdu, China; Department of Urology, Peking University First Hospital, Institute of Urology, National Urological Cancer Center of China, Peking University, Beijing, China; Department of Medical Oncology, Weifang People's Hospital, Weifang, China; Department of Urology, Hunan Cancer Hospital/The Affiliated Cancer Hospital of Xiangya School of Medicine of Central South University, Changsha, China; Department of Medical Oncology, Anhui Provincial Cancer Hospital, Hefei, China; RemeGen Co., Ltd., Yantai, Shandong, China; School of Life Science and Technology, Tongji University, Shanghai, China; Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Genitourinary Oncology, Peking University Cancer Hospital & Institute, Beijing, China
- Xinan Sheng
- Corresponding authors.; Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China; Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Renal Cancer and Melanoma, Peking University Cancer Hospital & Institute, Beijing, China; Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China; Department of Medical Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China; Department of Genitourinary Oncology, National Clinical Research Center for Cancer, Tianjin Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China; Department of Genitourinary Oncology, Chongqing University Cancer Hospital and Chongqing Cancer Institute and Chongqing Cancer Hospital, Chongqing, China; Department of Urology, Qilu Hospital of Shandong University, Jinan, China; Department of Biotherapy, Cancer Center, National Clinical Research Center for Geriatrics, West China Hospital of Sichuan University, Chengdu, China; Department of Urology, Peking University First Hospital, Institute of Urology, National Urological Cancer Center of China, Peking University, Beijing, China; Department of Medical Oncology, Weifang People's Hospital, Weifang, China; Department of Urology, Hunan Cancer Hospital/The Affiliated Cancer Hospital of Xiangya School of Medicine of Central South University, Changsha, China; Department of Medical Oncology, Anhui Provincial Cancer Hospital, Hefei, China; RemeGen Co., Ltd., Yantai, Shandong, China; School of Life Science and Technology, Tongji University, Shanghai, China; Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Genitourinary Oncology, Peking University Cancer Hospital & Institute, Beijing, China
- Aiping Zhou
- Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China; Corresponding authors.
- Jianming Ying
- Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China; Corresponding authors.
- Journal volume & issue
-
Vol. 3,
no. 2
pp. 121 – 128
Abstract
Background: Human epidermal growth factor receptor 2 (HER2) overexpression is related to anti-HER2 therapy in many tumors. RC48- antibody-drug conjugate (ADC) has shown promising efficacy in patients with HER2-positive locally advanced or metastatic urothelial carcinoma (UC). The characteristic expression and scoring systems of HER2 are nonexistent in UC. We aimed to explore HER2 status and its correlation with the efficacy of HER2-targeting ADC therapy in UC. Methods: A total of 137 and 43 patients were enrolled in cohort 1 and cohort 2, respectively, from March 2009 to December 2018. The patients in cohort 2 were enrolled in a phase II study of RC48-ADC. UC samples were tested for HER2 status using immunohistochemistry (IHC) and/or fluorescence in situ hybridization (FISH). The 2018 ASCO/CAP HER2 scoring system was adopted and modified to score HER2 expression in UC. Results: The HER2-positive (IHC 2+ or 3+) rate was 24.1% (33/137). In HER2 IHC 2+ or 3+ patients, the HER2 gene amplification rate was 31% (13/42). The objective response rates (ORRs) in RC48-ADC-treated patients with IHC 3+, IHC 2+ and FISH+, IHC 2+ and FISH- were 58.8%, 66.7% and 40%, respectively. The ORR showed a trend toward a better benefit for RC48-ADC therapy in patients with HER2 amplification than in those without amplification (61.5% vs. 44.8%, P = 0.059). The heterogeneity of HER2 expression in the primary tumor was 55.5% (15/27), and the ORR was not significantly different between patients with tumor heterogeneity and homogeneity. Conclusions: IHC testing should be performed to assess the HER2 status before the initiation of HER2-ADC therapy. There was a trend toward a better benefit for patients with HER2 amplification, and tumor heterogeneity did not influence the drug efficacy.
